A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E and Beta Carotene for Age-Related Cataract and Vision Loss: AREDS Report No. 9 | Cataract and Other Lens Disorders | JAMA Ophthalmology | JAMA Network
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Bunce  GEKinoshita  JHorwitz  J Nutritional factors in cataract [review].  Annu Rev Nutr. 1990;10233- 254Google ScholarCrossref
Taylor  A Cataract: relationships between nutrition and oxidation[review].  J Am Coll Nutr. 1993;12138- 146Google ScholarCrossref
Christen  WGGlynn  RJHennekens  CH Antioxidants and age-related eye disease current and future perspectives[review].  Ann Epidemiol. 1996;660- 66Google ScholarCrossref
Leske  MCChylack  LT  JrWu  SY The Lens Opacities Case-Control Study: risk factors for cataract.  Arch Ophthalmol. 1991;109244- 251Google ScholarCrossref
Leske  MCWu  SYConnell  AMSHyman  LSchachat  AP Lens opacities, demographic factors and nutritional supplements in the Barbados Eye Study.  Int J Epidemiol. 1997;261314- 1322Google ScholarCrossref
Mares-Perlman  JAKlein  BEKlein  RRitter  LL Relation between lens opacities and vitamin and mineral supplement use.  Ophthalmology. 1994;101315- 325Google ScholarCrossref
Robertson  JMDonner  APTrevithick  JR A possible role for vitamins C and E in cataract prevention.  Am J Clin Nutr. 1991;53suppl 1346S- 351SGoogle Scholar
Cumming  RGMitchell  PSmith  W Diet and cataract: The Blue Mountains Eye Study.  Ophthalmology. 2000;107450- 456Google ScholarCrossref
Mares-Perlman  JABrady  WEKlein  BE  et al.  Diet and nuclear lens opacities.  Am J Epidemiol. 1995;141322- 334Google ScholarCrossref
Mohan  MSperduto  RDAngra  SK  et al.  India-US case-control study of age-related cataracts.  Arch Ophthalmol. 1989;107670- 676Google ScholarCrossref
Jacques  PFChylack  LT  Jr Epidemiologic evidence of a role for the antioxidant vitamins and carotenoids in cataract prevention.  Am J Clin Nutr. 1991;53(suppl 1)352S- 355SGoogle Scholar
Tavani  ANegri  ELa Vecchia  C Food and nutrient intake and risk of cataract.  Ann Epidemiol. 1996;641- 46Google ScholarCrossref
Vitale  SWest  SHallfrisch  J  et al.  Plasma antioxidants and risk of cortical and nuclear cataract.  Epidemiology. 1993;4195- 203Google ScholarCrossref
Jacques  PFChylack  LT  JrMcGandy  RBHartz  SC Antioxidant status in persons with and without senile cataract.  Arch Ophthalmol. 1988;106337- 340Google ScholarCrossref
Leske  CLWu  SYHyman  L  et al. for the Lens Opacities Case-Control Study Group, Biochemical factors in the lens opacities: case-control study.  Arch Ophthalmol. 1995;1131113- 1119Google ScholarCrossref
Knekt  PHeliövaara  MRissanen  AAromaa  AAaran  RK Serum antioxidant vitamins and risk of cataract.  BMJ. 1992;3051392- 1394Google ScholarCrossref
Hankinson  SEStampfer  MJSeddon  JM  et al.  Nutrient intake and cataract extraction in women: a prospective study.  BMJ. 1992;305335- 339Google ScholarCrossref
Chasan-Taber  LWillett  WCSeddon  JM  et al.  A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women.  Am J Clin Nutr. 1999;70509- 516Google Scholar
Seddon  JMChristen  WGManson  JE  et al.  The use of vitamin supplements and the risk of cataract among US male physicians.  Am J Public Health. 1994;84788- 792Google ScholarCrossref
Brown  LRimm  EBSeddon  JM  et al.  A prospective study of carotenoid intake and risk of cataract extraction in US men.  Am J Clin Nutr. 1999;70517- 524Google Scholar
Lyle  BJMares-Perlman  JAKlein  BEKlein  RGreger  JL Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study.  Am J Epidemiol. 1999;149801- 809Google ScholarCrossref
Leske  MCChylack  LT  JrHe  Q  et al.  Antioxidant vitamins and nuclear opacities: the longitudinal study of cataract.  Ophthalmology. 1998;105831- 836Google ScholarCrossref
The Italian-American Cataract Study Group, Risk factors for age-related cortical, nuclear, and posterior subcapsular cataracts.  Am J Epidemiol. 1991;133541- 553Google Scholar
McCarty  CAMukesh  BNFu  CLTaylor  HR The epidemiology of cataract in Australia.  Am J Ophthalmol. 1999;128446- 465Google ScholarCrossref
Mares-Perlman  JALyle  BJKlein  R  et al.  Vitamin supplement use and incident cataracts in a population-based study.  Arch Ophthalmol. 2000;1181556- 1563Google ScholarCrossref
Rouhiainen  PRouhiainen  HSalonen  JT Association between low plasma vitamin E concentration and progression of early cortical lens opacities.  Am J Epidemiol. 1996;144496- 500Google ScholarCrossref
Nadalin  GRobman  LDMcCarty  CAGarrett  SKMcNeil  JJTaylor  HR The role of past intake of vitamin E in early cataract changes.  Ophthalmic Epidemiol. 1999;6105- 112Google ScholarCrossref
Teikari  JVirtamo  JRautalahti  MPalmgren  JLiesto  KHeinonen  OP Long-term supplementation with alpha-tocopherol and beta-carotene and age-related cataract.  Acta Ophthalmol Scand. 1997;75634- 640Google ScholarCrossref
Sperduto  RDHu  TSMilton  RC  et al.  The Linxian Cataract Studies: two nutritional intervention trials.  Arch Ophthalmol. 1993;1111246- 1253Google ScholarCrossref
Christen  WG Beta-carotene and age-related cataract in a randomized trial of U.S. physicians [ARVO abstract].  Invest Ophthalmol Vis Sci. 2001;42S518Abstract 2790.Google Scholar
Robman  LDMcCarty  CATikellis  G  et al.  VECAT Study: The effect of vitamin E on the progression of lens opacities: preliminary results [ARVO abstract].  Invest Ophthalmol Vis Sci. 2001;42S508Abstract 2742.Google Scholar
Sperduto  RDFerris  FL  IIIKurinij  N Do we have a nutritional treatment for age-related cataract or macular degeneration [editorial]?  Arch Ophthalmol. 1990;1081403- 1405Google ScholarCrossref
The Age-Related Eye Disease Study Research Group, The Age-Related Eye Disease Study (AREDS): design implications: AREDS Report No. 1.  Control Clin Trials. 1999;20573- 600Google ScholarCrossref
The Age-Related Eye Disease Study Research Group, The Age-Related Eye Disease Study (AREDS) system for classifying cataracts from photographs: AREDS Report No. 4.  Am J Ophthalmol. 2001;131167- 175Google ScholarCrossref
Mangione  CMLee  PPGutierrez  PRSpritzer  KBerry  SHays  RD Development of the 25-item National Eye Institute Visual Function Questionnaire.  Arch Ophthalmol. 2001;1191050- 1058Google ScholarCrossref
McCarty  CALee  SELivingston  PMBissinella  MTaylor  HR Ocular exposure to UV-B in sunlight: the Melbourne visual impairment project model.  Bull World Health Organ. 1996;74353- 360Google Scholar
Lan  KKLachin  JM Implementation of group sequential logrank tests in a maximum duration trial.  Biometrics. 1990;46759- 770Google ScholarCrossref
O'Brien  PCFleming  TR A multiple testing procedure for clinical trials.  Biometrics. 1979;35549- 556Google ScholarCrossref
Pocock  SJ Group sequential methods in the design and analysis of clinical trials.  Biometrika. 1977;64191- 199Google ScholarCrossref
The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group, The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers.  N Engl J Med. 1994;3301029- 1035Google ScholarCrossref
Omenn  GSGoodman  GEThornquist  MD  et al.  Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease.  N Engl J Med. 1996;3341150- 1155Google ScholarCrossref
Alaimo  KMcDowell  MABriefel  RR  et al.  Dietary intake of vitamins, minerals, and fiber of persons ages 2 months and over in the United States: Third National Health and Nutrition Examination Survey, Phase 1, 1988-91.  Adv Data. 1994;2581- 28Google Scholar
Bone  RALandrum  JTTarsis  SL Preliminary identification of the human macular pigment.  Vision Res. 1985;251531- 1535Google ScholarCrossref
Yeum  KJTaylor  ATang  GRussell  RM Measurement of carotenoids, retinoids, and tocopherols in human lenses.  Invest Ophthalmol Vis Sci. 1995;362756- 2761Google Scholar
Garrett  SKMcNeil  JJSilagy  C  et al.  Methodology of the VECAT study: vitamin E intervention in cataract and age-related macular degeneration.  Ophthalmic Epidemiol. 1999;6195- 208Google ScholarCrossref
Christen  WGGaziano  MHennekens  CH Design of Physicians' Health Study II: a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials [review].  Ann Epidemiol. 2000;10125- 134Google ScholarCrossref
Manson  JEGaziano  JMSpelsberg  A  et al. for the WACS Research Group, A secondary prevention trial of antioxidant vitamins and cardiovascular disease in women: rationale, design, and methods.  Ann Epidemiol. 1995;5261- 269Google ScholarCrossref
Buring  JEHennekens  CH The Women's Health Study: summary of the study design.  J Myocardial Ischemia. 1992;427- 29Google Scholar
Chylack  LT  JrWolfe  JKFriend  J  et al.  Validation of methods for the assessment of cataract progression in the Roche European-American Anticataract Trial (REACT).  Ophthalmic Epidemiol. 1995;259- 75Google ScholarCrossref
Clinical Sciences
October 2001

A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E and Beta Carotene for Age-Related Cataract and Vision Loss: AREDS Report No. 9

Age-Related Eye Disease Study Research Group
Author Affiliations

The AREDS investigators have no commercial or proprietary interest in the supplements used in this study.

Arch Ophthalmol. 2001;119(10):1439-1452. doi:10.1001/archopht.119.10.1439

Background  Experimental and observational data suggest that micronutrients with antioxidant capabilities may retard the development of age-related cataract.

Objective  To evaluate the effect of a high-dose antioxidant formulation on the development and progression of age-related lens opacities and visual acuity loss.

Design  The 11-center Age-Related Eye Disease Study (AREDS) was a double-masked clinical trial. Participants were randomly assigned to receive daily oral tablets containing either antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) or no antioxidants. Participants with more than a few small drusen were also randomly assigned to receive tablets with or without zinc (80 mg of zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as part of the age-related macular degeneration trial. Baseline and annual (starting at year 2) lens photographs were graded at a reading center for the severity of lens opacities using the AREDS cataract grading scale.

Main Outcome Measures  Primary outcomes were (1) an increase from baseline in nuclear, cortical, or posterior subcapsular opacity grades or cataract surgery, and (2) at least moderate visual acuity loss from baseline (≥15 letters). Primary analyses used repeated-measures logistic regression with a statistical significance level of P = .01. Serum level measurements, medical histories, and mortality rates were used for safety monitoring.

Results  Of 4757 participants enrolled, 4629 who were aged from 55 to 80 years had at least 1 natural lens present and were followed up for an average of 6.3 years. No statistically significant effect of the antioxidant formulation was seen on the development or progression of age-related lens opacities (odds ratio = 0.97, P = .55). There was also no statistically significant effect of treatment in reducing the risk of progression for any of the 3 lens opacity types or for cataract surgery. For the 1117 participants with no age-related macular degeneration at baseline, no statistically significant difference was noted between treatment groups for at least moderate visual acuity loss. No statistically significant serious adverse effect was associated with treatment.

Conclusion  Use of a high-dose formulation of vitamin C, vitamin E, and beta carotene in a relatively well-nourished older adult cohort had no apparent effect on the 7-year risk of development or progression of age-related lens opacities or visual acuity loss.