0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Age-Related Cataract in Men in the Selenium and Vitamin E Cancer Prevention Trial Eye Endpoints Study A Randomized Clinical Trial FREE

William G. Christen, ScD1; Robert J. Glynn, ScD1; J. Michael Gaziano, MD1,2,3; Amy K. Darke, MS4; John J. Crowley, PhD4; Phyllis J. Goodman, MS4; Scott M. Lippman, MD5; Thomas E. Lad, MD6; James D. Bearden, MD7; Gary E. Goodman, MD8; Lori M. Minasian, MD9; Ian M. Thompson Jr, MD10; Charles D. Blanke, MD11; Eric A. Klein, MD12
[+] Author Affiliations
1Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
2Division of Aging, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
3Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, Massachusetts
4Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington
5Office of the Director, Moores Cancer Center, University of California at San Diego
6Jesse Brown VA Medical Center, Chicago, Illinois
7Upstate Carolina Community Clinical Oncology Program/Spartanburg Regional Medical Center, Spartanburg, South Carolina
8Medical Oncology, Swedish Medical Center, Seattle, Washington
9Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland
10Department of Urology, Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio
11Southwest Oncology Group Chair’s Office, Knight Cancer Institute, Oregon Health and Sciences University, Portland
12Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
JAMA Ophthalmol. 2015;133(1):17-24. doi:10.1001/jamaophthalmol.2014.3478.
Text Size: A A A
Published online

Importance  Observational studies suggest a role for dietary nutrients such as vitamin E and selenium in cataract prevention. However, the results of randomized clinical trials of vitamin E supplements and cataract have been disappointing and are not yet available for selenium.

Objective  To test whether long-term supplementation with selenium and vitamin E affects the incidence of cataract in a large cohort of men.

Design, Setting, and Participants  The Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study was an ancillary study of the Southwest Oncology Group–coordinated SELECT, a randomized placebo-controlled 4-arm trial of selenium and vitamin E conducted among 35 533 men, 50 years and older for African American participants and 55 years and older for all other men, at 427 participating sites in the United States, Canada, and Puerto Rico. A total of 11 267 SELECT participants from 128 SELECT sites participated in the SELECT Eye Endpoints ancillary study.

Interventions  Individual supplements of selenium (200 μg per day from L-selenomethionine) and vitamin E (400 IU per day of all rac-α-tocopheryl acetate).

Main Outcomes and Measures  Incident cataract was defined as a lens opacity, age related in origin, and responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-reports confirmed by medical record review. Cataract extraction was defined as the surgical removal of an incident cataract.

Results  During a mean (SD) of 5.6 (1.2) years of treatment and follow-up, 389 cases of cataract were documented. There were 185 cataracts in the selenium group and 204 in the no selenium group (hazard ratio, 0.91; 95 % CI, 0.75-1.11; P = .37). For vitamin E, there were 197 cases in the treated group and 192 in the placebo group (hazard ratio, 1.02; 95 % CI, 0.84-1.25; P = .81). Similar results were observed for cataract extraction.

Conclusions and Relevance  These data from a large cohort of apparently healthy men indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age-related cataract.

Trial Registration  ClinicalTrials.gov Identifier: NCT00784225

Figures in this Article

Basic research and animal studies suggest a potential role for dietary nutrients in cataract onset and progression.13 Vitamin E and selenium are of particular interest among examined nutrients because both are found in the human lens4,5 and plausible mechanisms have been previously described. Vitamin E is a lipid-soluble antioxidant concentrated in lens fibers and membranes and may inhibit cataract formation by reducing photoperoxidation of lens lipids and stabilizing lens cell membranes.68 Selenium is a trace element incorporated into the endogenous antioxidant enzyme glutathione peroxidase, which is found in high concentrations in the lens, particularly in peripheral lens fiber cells where glutathione is synthesized.9 Glutathione peroxidase acts to protect membrane lipids and macromolecules from peroxide-induced oxidative damage1,1012 and its activity is positively correlated with selenium concentration.1315 Selenium has also been shown to inhibit oxidative stress-induced apoptosis in lens epithelial cells.16

Observational studies in humans generally indicate lower rates of cataract in persons with higher dietary intake or blood levels of selenium (or glutathione peroxidase) and, in particular, vitamin E.4,1721 However, the results of randomized trials have been disappointing. Seven trials testing high-dose vitamin E supplements, either alone or in combination with other vitamin supplements, in generally well-nourished populations have found few benefits on cataract for treatment durations as long as 8 years in men and 10 years in women.2228 For selenium, randomized clinical trial data are limited. Selenium was included in a multivitamin/mineral combination associated with a lower risk of cataract in a nutritionally deficient population in China23 and in well-nourished populations in Italy29 and the United States.30 However, the individual effect of selenium on cataract occurrence could not be determined in those trials.

Herein, we report the findings for cataract from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints (SEE) Study. The SEE study was an ancillary study of the SELECT, a randomized placebo-controlled 4-arm trial of selenium, vitamin E, and the combination of selenium and vitamin E in prostate cancer prevention. To our knowledge, the data reported here represent the first trial data for the individual effect of selenium in cataract prevention.

Study Design
The Selenium and Vitamin E Cancer Prevention Trial

All men provided written informed consent for participation in the SELECT and the local institutional review board of each study site approved the SELECT for activation and reviewed its progress annually. Detailed descriptions of the rationale, design, and conduct of the SELECT have been previously published.31,32 The SELECT was a phase 3 randomized placebo-controlled 4-arm trial of selenium (200 μg per day from L-selenomethionine), vitamin E (400 IU per day of all rac-α-tocopheryl acetate), and the combination of selenium and vitamin E for the prevention of prostate cancer among 35 533 men 50 years and older for African American men and 55 and older for all other men.32 Eligible men had no prior diagnosis of prostate cancer, 4 ng/mL or less of prostate-specific antigen in serum, and a digital rectal examination not suspicious for cancer. Eligible men also reported no current use of anticoagulant therapy other than 175 mg or less per day of acetylsalicylic acid or 81 mg or less per day of acetylsalicylic acid with clopidogrel bisulfate, no history of hemorrhagic stroke, and normal blood pressure. Men were offered a free multivitamin containing no selenium or vitamin E (to increase adherence) and were required to avoid over-the-counter supplements of selenium and vitamin E throughout the study. Men were randomized in a randomized block scheme in which the block was the study site. This ensured a balance of the 4 intervention groups within each study site.

The SELECT was activated in July 25, 2001, with planned follow-up of 7 to 12 years. Participant clinic visits were scheduled every 6 months throughout the trial. On diagnosis of prostate cancer, participants were followed up at annual clinic visits. At study visits, men were asked about new medical events, including diagnosis of cataract or cataract surgery in the previous 6 months. Adherence and adverse events were monitored every 6 months and a limited physical examination, including assessments of blood pressure, weight, and smoking status, was conducted annually. The trial was terminated early on October 23, 2008, because of lack of efficacy in prostate cancer prevention and the observation of possible adverse events (ie, small and not statistically significant increases in type 2 diabetes mellitus in the selenium [alone] group and prostate cancer incidence in the vitamin E [alone] group); with longer follow-up, those taking vitamin E alone had a 17% increased risk of prostate cancer.33

The SEE Study

The SEE study was an ancillary study of the SELECT that began on September 1, 2003, with funding from the National Eye Institute. Participation in the SEE ancillary study was voluntary. Of 427 SELECT study sites in the United States, Canada, and Puerto Rico, 148 sites obtained local review board approval to participate in the SEE study. Of these, 104 sites registered at least 1 participant to the SEE study. Twenty-four of the remaining 44 sites did not register any participants to the SEE study but maintained current institutional review board approval and are included in the denominator. Thus, this report includes data from 128 sites comprising 11 267 SELECT participants (Figure 1). The characteristics of men who participated in the SEE study did not differ from those of the overall SELECT population (data not shown).

Place holder to copy figure label and caption
Figure 1.
CONSORT Flow Diagram for the Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints (SEE) Study

Primary comparisons examine the main effects of the SELECT supplements (selenium vs no selenium, vitamin E vs no vitamin E) on occurrence of cataract.

Graphic Jump Location
End Point Assessment

Men who reported a prior diagnosis of cataract at baseline in the SELECT were not eligible and were excluded from analysis. At their first visit after approval and activation at their sites, men were asked to report new events, including cataract diagnosis or extraction since entering the SELECT. In subsequent 6-month visits, men reported new events since their last visit. Following a report of cataract, participants were asked to provide written informed consent for participation in the SEE study and written consent to obtain relevant medical records. The completed medical record release form was faxed to the SEE study center in Boston, Massachusetts, which then contacted ophthalmologists and optometrists by mail and requested them to complete a cataract questionnaire or, alternatively, supply copies of the relevant medical records.

The cataract questionnaire asked about the presence of lens opacities, diagnosis date, visual acuity loss, cataract extraction, other ocular abnormalities, and cataract type (eg, nuclear sclerosis, cortical, or posterior subcapsular) and origin (including age related, traumatic, congenital, inflammatory, or surgery induced or steroid induced).

The primary end point was incident cataract, defined as a lens opacity diagnosed after randomization but before October 23, 2008, age related in origin, and best-corrected visual acuity of 20/30 or worse attributable to the opacity. Cataract extraction was a secondary end point and was defined as the surgical removal of an incident cataract.

Statistical Analysis

The SEE study was designed with 4 prespecified comparisons to assess the main effects of the 2 study agents (selenium ± vitamin E vs no selenium ± vitamin E; vitamin E ± selenium vs no vitamin E ± selenium) on the primary end points of incident cataract and visually significant age-related macular degeneration. For each comparison, the prespecified significance level was set at P < .05. To adjust for multiple comparisons, we applied the Bonferroni correction and considered 0.0125 (0.05/4) statistically significant.

Men were classified according to their randomized selenium or vitamin E treatment assignment and were followed up until the occurrence of cataract, death, or loss to follow-up. Men who reported cataract but did not register in the SEE study were censored as of the date of their cataract report. With 389 confirmed events, the study had adequate power (80%) to detect a 25% reduction in the hazard of incident cataract.

We compared baseline characteristics in the selenium and vitamin E groups using 2-sample t tests, χ2 tests for proportions, and tests for trend for ordinal categories. Kaplan-Meier curves estimated cumulative incidence across time by randomized group and curves were compared using the log-rank test. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of cataract comparing treated and nontreated groups after adjustment for the other treatment assignment (selenium or vitamin E). Models were also fit separately within the following 4 age groups: 50 to 54 years, 55 to 64 years, 65 to 74 years, and 75 or older. Tests of trend were calculated by including a term for the interaction of the antioxidant and age (expressed as a continuous variable with values 1 to 4 corresponding to the 4 age groups) in a proportional hazards model. Interaction terms were used to test for additivity of the 2 antioxidant agents using multiplicative terms in the Cox model. We tested the proportional hazards assumption by modeling interaction terms separately for selenium or vitamin E with the logarithm of time and these assumptions were not violated (P > .05). For each HR, the 95 % CI and 2-sided P values were calculated.

We also analyzed subgroup data by categories of baseline variables that were possible risk factors for cataract. We explored possible effect modification by using interaction terms between subgroup indicators and treatment assignment and we tested for trend when subgroup categories were ordinal.

In secondary analyses, Cox models were used to calculate HRs of cataract, comparing event rates in the active treatment arms (selenium alone, vitamin E alone, and selenium and vitamin E) with the rate in the placebo group.

Individuals were the unit of analysis because eyes were not examined independently and we classified individuals according to the status of the worse eye, as defined by disease severity. When the worse eye was excluded because of visual acuity loss attributed to other ocular abnormalities, the fellow eye was considered for classification. Data were analyzed using SAS version 9.2 (SAS Institute Inc).

The distribution of baseline characteristics of SEE study participants that are possible risk factors for cataract is shown in Table 1. As expected in this large randomized trial, the characteristics were distributed evenly between active and placebo groups for selenium and vitamin E.

Table Graphic Jump LocationTable 1.  Baseline Characteristics by Randomized Groups in the Selenium and Vitamin E Cancer Prevention Trial Eye Endpoints Study

During a mean (SD) follow-up of 5.6 (1.2) years, a total of 389 cataracts and 219 cataract extractions were confirmed through medical record review.

Selenium

There were 185 cataracts in the selenium group and 204 in the no selenium group (HR, 0.91; 95% CI, 0.75-1.11; P = .37) (Table 2). In age-stratified analyses, HRs tended to be lowest in the older age groups, although a test of trend did not attain statistical significance. For cataract extraction, there were 99 cases in the selenium group and 120 in the no selenium group (HR, 0.84; 95% CI, 0.64-1.09; P = .19) (Table 2). As observed for diagnosed cataract, HRs for extraction tended to be lowest in the older age groups, although the test of trend was not significant.

Table Graphic Jump LocationTable 2.  Confirmed Cases of Age-Related Cataract and Cataract Extraction According to Randomized Treatment Assignment in 4 Age Groups

Cumulative incidence rate of cataract and cataract extraction by randomized selenium according to year of follow-up are shown in Figure 2. For the primary end point of cataract, there was no apparent benefit of selenium at any point during the trial. For cataract extraction, curves appeared to diverge at 5 to 6 years of follow-up but never attained statistical significance.

Place holder to copy figure label and caption
Figure 2.
Cumulative Incidence Rates of Cataract and Cataract Extraction by Randomized Selenium Assignment in the Selenium and Vitamin E Cancer Prevention Trial Eye Endpoints Study
Graphic Jump Location

The effect of selenium on cataract diagnosis did not differ markedly within categories of known or possible risk factors (eTable in the Supplement).

Vitamin E

There were 197 cataracts in the vitamin E group and 192 in the no vitamin E group (HR, 1.02; 95% CI, 0.84-1.25; P = .81) (Table 2). The HRs did not vary significantly among the 4 age groups. For cataract extraction, there were 114 cases in the vitamin E group and 105 in the no vitamin E group (HR, 1.08; 95% CI, 0.83-1.41; P = .58) (Table 2).

Cumulative incidence curves for cataract and cataract extraction by randomized vitamin E are shown in Figure 3. For both end points, there was no apparent effect of vitamin E at any point during the trial.

Place holder to copy figure label and caption
Figure 3.
Cumulative Incidence Rates of Cataract and Cataract Extraction by Randomized Vitamin E Assignment in the Selenium and Vitamin E Cancer Prevention Trial Eye Endpoints Study
Graphic Jump Location

The lack of effect of vitamin E on cataract diagnosis did not differ markedly within categories of known or possible risk factors (eTable in the Supplement).

Secondary Comparisons

There were no significant differences in the rates of cataract or cataract extraction between the 4 treatment groups. Compared with placebo, HRs for cataract were 0.82 (95% CI, 0.62-1.09; P = .18) in the selenium alone group, 0.93 (95% CI, 0.71-1.22; P = .61) in the vitamin E alone group, and 0.94 (95% CI, 0.71-1.23; P = .65) in the selenium and vitamin E group (P for interaction = .32). For cataract extraction, HRs were 0.73 (95% CI, 0.50-1.08; P = .11) in the selenium alone group, 0.96 (95% CI, 0.67-1.38; P = .83) in the vitamin E alone group, and 0.91 (95% CI, 0.63-1.31; P = .60) in the selenium and vitamin E group (P for interaction = .35).

In this large randomized trial of apparently healthy men, middle-aged and older, daily supplementation with selenium and/or vitamin E for an average of 5.6 years had no significant effect on diagnosed cataract, the primary study end point, or cataract extraction. In our primary main-effects analysis, men assigned selenium (±vitamin E) or selenium (with or without vitamin E) had a nonsignificant 9% reduction in diagnosed cataract and a nonsignificant 16% reduction in cataract extraction. The 95% CIs around these estimates excluded with reasonable certainty beneficial effects of 25% or more for diagnosed cataract and 36% or more for cataract extraction. For vitamin E (±selenium) or vitamin E (with or without selenium), HRs for both diagnosed cataract and extraction were near the null value of 1.0 and the 95% CIs excluded with reasonable certainty beneficial effects more than 17% for each end point.

To our knowledge, the SEE study is the first randomized trial to assess the separate effect of selenium supplementation in cataract prevention. While the overall main-effects analysis indicated a nonsignificant 9% lower risk of cataract for men in the selenium (±vitamin E) or selenium (with or without vitamin E) group, the reduction was somewhat more (18%), although still nonsignificant when we compared men in the selenium alone arm with the placebo arm. Three previous trials examined selenium as a component of a multivitamin/multimineral supplement in cataract prevention but the separate effect of selenium could not be determined in those trials. In the Linxian cataract study, end-of-trial eye examinations conducted among a subset of participants with esophageal dysplasia indicated a reduced prevalence of nuclear cataract in participants aged 65 to 74 years who were randomly assigned to a daily vitamin/mineral supplement that included selenium (50 μg) compared with the placebo (odds ratio, 0.57; 95% CI, 0.36-0.90).23 In a second double-blind single-center clinical trial of 1020 participants aged 55 to 75 years, persons randomized to a daily multivitamin that included selenium (25 μg) compared with placebo had a significant 18% reduction in cataract development or progression after 9 years of treatment.29 Finally, recent results from the Physicians’ Health Study II indicated a significant 9% lower risk of cataract (HR, 0.91; 95% CI, 0.83-0.99) for men assigned a daily multivitamin that included selenium (20 μg) compared with placebo after 11 years of treatment.30 Our findings in the SEE study extend these prior findings by showing that selenium, alone or in combination with vitamin E, is not likely to have a large beneficial effect on cataract, although a smaller but potentially important benefit cannot be ruled out.

Our null findings for vitamin E in cataract prevention are consistent with the overall negative findings in previous randomized trials and, in particular, with 4 trials designed to estimate the individual effect of vitamin E supplementation. These include a trial of 29 133 Finnish male smokers treated with daily vitamin E (50 mg) for 5.7 years,22 a trial of 1193 men and women treated with daily vitamin E (500 IU) for 4 years,26 a trial of 39 876 female health professionals treated with alternate-day vitamin E (600 IU) for 10 years,27 and a trial of 11 545 male physicians treated with alternate-day vitamin E (400 IU) for 8 years.28 Our findings in the SEE study, based on an average of 5.5 years of treatment and follow-up, are consistent with these prior findings and add to the total body of evidence, showing that long-term supplementation with high-dose vitamin E has no material impact on cataract development or progression in men or women.

Previous studies have shown that vitamin E interacts with selenium and glutathione peroxidase to prevent the formation of oxidative products of polyunsaturated fatty acids and oxidative damage.34,35 Other studies have shown that selenium-dependent glutathione peroxidase reduces hydroperoxides formed by the scavenging action of vitamin E36 and may function indirectly by maintaining vitamin E (and vitamin C) in its reduced and functional form.37 However, we found no evidence of a significant interaction of selenium and vitamin E in risk of cataract or cataract extraction.

Several possible limitations of the trial need to be considered, particularly in view of the negative findings. An inadequate dosage of study agents seems unlikely. The dose of vitamin E (400 IU per day [equivalent to 400 mg per day] of all rac-α-tocopheryl acetate) was more than 26 times the recommended daily intake of 15 mg38 and previous observational studies reported benefits with a median intake of 12 mg of vitamin E.39 The dose of selenium (200 μg/d from L-selenomethionine) was based on efficacy and safety data31,32 and was approximately 4 times the recommended dietary allowance for adults in North American.40 Inadequate duration of treatment also seems unlikely, particularly for vitamin E because results from the Women’s Health Study27 and Physicians’ Health Study II28 indicated no benefit of vitamin E on cataract, even with treatment durations 3 to 4 years longer than that in the SEE study. Random misclassification of cataract was reduced by the use of medical record data to confirm self-reports. Nonrandom or differential misclassification was unlikely because medical records were reviewed without knowledge of treatment assignment. Informative censoring, which would have occurred if dropouts or missing data were related to occurrence of cataract, also seems unlikely. Adherence is a concern in any long-term trial but adherence determined by pill count remained consistently good during follow-up, averaging 83% at year 1 and 65% at year 5. Finally, these findings in men may not be applicable to women.

These randomized trial data from a large cohort of apparently healthy men indicate that long-term daily supplemental use of vitamin E has no material impact on cataract incidence. The data also exclude any large beneficial effect on cataract for long-term supplemental use of selenium, with or without vitamin E, although a smaller but potentially important beneficial effect could not be ruled out.

Corresponding Author: William G. Christen, ScD, Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Ave E, Boston, MA 02215-1204 (wchristen@rics.bwh.harvard.edu).

Submitted for Publication: February 11, 2014; final revision received April 28, 2014; accepted April 29, 2014.

Published Online: September 18, 2014. doi:10.1001/jamaophthalmol.2014.3478.

Author Contributions: Dr Christen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Christen, Lippman, G. E. Goodman, Minasian.

Acquisition, analysis, or interpretation of data: Christen, Glynn, Gaziano, Darke, Crowley, P. J. Goodman, Lippman, Lad, Bearden, G. E. Goodman, Thompson, Blanke, Klein.

Drafting of the manuscript: Christen, Lippman.

Critical revision of the manuscript for important intellectual content: Glynn, Gaziano, Darke, Crowley, P. J. Goodman, Lippman, Lad, Bearden, G. E. Goodman, Minasian, Thompson, Blanke, Klein.

Statistical analysis: Glynn, Darke, P. J. Goodman.

Obtained funding: Christen, Crowley, Lippman, Klein.

Administrative, technical, or material support: Christen, Gaziano, Lippman, Bearden, G. E. Goodman, Minasian, Thompson, Blanke, Klein.

Study supervision: Christen, P. J. Goodman, G. E. Goodman, Minasian.

Conflict of Interest Disclosures: Dr Gaziano received study support and a speaking honorarium from Pfizer related to vitamins. No other disclosures were reported.

Funding/Support: This work was supported by grant EY014418 and in part by grant CA37429 from the Public Health Service Cooperative Agreement awarded by the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and the National Center for Complementary and Alternative Medicine.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Information: Study agents and packaging were provided by Sabinsa Corporation, Tishcon Corporation, and DSM Nutritional Products, Inc. Optional study multivitamins were provided by Perrigo Company.

Gerster  H.  Antioxidant vitamins in cataract prevention. Z Ernahrungswiss. 1989;28(1):56-75.
PubMed   |  Link to Article
Bunce  GE, Kinoshita  J, Horwitz  J.  Nutritional factors in cataract. Annu Rev Nutr. 1990;10:233-254.
PubMed   |  Link to Article
Varma  SD, Devamanoharan  PS, Morris  SM.  Prevention of cataracts by nutritional and metabolic antioxidants. Crit Rev Food Sci Nutr. 1995;35(1-2):111-129.
PubMed   |  Link to Article
Rasi  V, Costantini  S, Moramarco  A, Giordano  R, Giustolisi  R, Balacco Gabrieli  C.  Inorganic element concentrations in cataractous human lenses. Ann Ophthalmol. 1992;24(12):459-464.
PubMed
Yeum  KJ, Shang  FM, Schalch  WM, Russell  RM, Taylor  A.  Fat-soluble nutrient concentrations in different layers of human cataractous lens. Curr Eye Res. 1999;19(6):502-505.
PubMed   |  Link to Article
Varma  SD, Beachy  NA, Richards  RD.  Photoperoxidation of lens lipids: prevention by vitamin E. Photochem Photobiol. 1982;36(6):623-626.
PubMed   |  Link to Article
Libondi  T, Menzione  M, Auricchio  G.  In vitro effect of alpha-tocopherol on lysophosphatidylcholine-induced lens damage. Exp Eye Res. 1985;40(5):661-666.
PubMed   |  Link to Article
Karslioglu  I, Ertekin  MV, Koçer  I,  et al.  Protective role of intramuscularly administered vitamin E on the levels of lipid peroxidation and the activities of antioxidant enzymes in the lens of rats made cataractous with gamma-irradiation. Eur J Ophthalmol. 2004;14(6):478-485.
PubMed
Giblin  FJ.  Glutathione: a vital lens antioxidant. J Ocul Pharmacol Ther. 2000;16(2):121-135.
PubMed   |  Link to Article
Yung  LM, Leung  FP, Yao  X, Chen  ZY, Huang  Y.  Reactive oxygen species in vascular wall. Cardiovasc Hematol Disord Drug Targets. 2006;6(1):1-19.
PubMed   |  Link to Article
Arthur  JR.  The glutathione peroxidases. Cell Mol Life Sci. 2000;57(13-14):1825-1835.
PubMed
Patching  SG, Gardiner  PH.  Recent developments in selenium metabolism and chemical speciation: a review. J Trace Elem Med Biol. 1999;13(4):193-214.
PubMed   |  Link to Article
Alfthan  G, Aro  A, Arvilommi  H, Huttunen  JK.  Selenium metabolism and platelet glutathione peroxidase activity in healthy Finnish men: effects of selenium yeast, selenite, and selenate. Am J Clin Nutr. 1991;53(1):120-125.
PubMed
Nève  J.  Human selenium supplementation as assessed by changes in blood selenium concentration and glutathione peroxidase activity. J Trace Elem Med Biol. 1995;9(2):65-73.
PubMed   |  Link to Article
Levander  OA, Alfthan  G, Arvilommi  H,  et al.  Bioavailability of selenium to Finnish men as assessed by platelet glutathione peroxidase activity and other blood parameters. Am J Clin Nutr. 1983;37(6):887-897.
PubMed
Zhu  X, Guo  K, Lu  Y.  Selenium effectively inhibits 1,2-dihydroxynaphthalene-induced apoptosis in human lens epithelial cells through activation of PI3-K/Akt pathway. Mol Vis. 2011;17:2019-2027.
PubMed
Knekt  P, Heliövaara  M, Rissanen  A, Aromaa  A, Aaran  RK.  Serum antioxidant vitamins and risk of cataract. BMJ. 1992;305(6866):1392-1394.
PubMed   |  Link to Article
Jacques  PF, Chylack  LT  Jr, McGandy  RB, Hartz  SC.  Antioxidant status in persons with and without senile cataract. Arch Ophthalmol. 1988;106(3):337-340.
PubMed   |  Link to Article
Jacques  PF, Hartz  SC, Chylack  LT  Jr, McGandy  RB, Sadowski  JA.  Nutritional status in persons with and without senile cataract: blood vitamin and mineral levels. Am J Clin Nutr. 1988;48(1):152-158.
PubMed
Chiu  CJ, Taylor  A.  Nutritional antioxidants and age-related cataract and maculopathy. Exp Eye Res. 2007;84(2):229-245.
PubMed   |  Link to Article
Karaküçük  S, Ertugrul Mirza  G, Faruk Ekinciler  O, Saraymen  R, Karaküçük  I, Ustdal  M.  Selenium concentrations in serum, lens and aqueous humour of patients with senile cataract. Acta Ophthalmol Scand. 1995;73(4):329-332.
PubMed   |  Link to Article
Teikari  JM, Rautalahti  M, Haukka  J,  et al.  Incidence of cataract operations in Finnish male smokers unaffected by alpha tocopherol or beta carotene supplements. J Epidemiol Community Health. 1998;52(7):468-472.
PubMed   |  Link to Article
Sperduto  RD, Hu  TS, Milton  RC,  et al.  The Linxian cataract studies: two nutrition intervention trials. Arch Ophthalmol. 1993;111(9):1246-1253.
PubMed   |  Link to Article
Age-Related Eye Disease Study Research Group.  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. Arch Ophthalmol. 2001;119(10):1439-1452.
PubMed   |  Link to Article
Chylack  LT  Jr, Brown  NP, Bron  A,  et al.  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. Ophthalmic Epidemiol. 2002;9(1):49-80.
PubMed   |  Link to Article
McNeil  JJ, Robman  L, Tikellis  G, Sinclair  MI, McCarty  CA, Taylor  HR.  Vitamin E supplementation and cataract: randomized controlled trial. Ophthalmology. 2004;111(1):75-84.
PubMed   |  Link to Article
Christen  WG, Glynn  RJ, Chew  EY, Buring  JE.  Vitamin E and age-related cataract in a randomized trial of women. Ophthalmology. 2008;115(5):822-829, e1.
PubMed   |  Link to Article
Christen  WG, Glynn  RJ, Sesso  HD,  et al.  Age-related cataract in a randomized trial of vitamins E and C in men. Arch Ophthalmol. 2010;128(11):1397-1405.
PubMed   |  Link to Article
Maraini  G, Williams  SL, Sperduto  RD,  et al; Clinical Trial of Nutritional Supplements and Age-Related Cataract Study Group.  A randomized, double-masked, placebo-controlled clinical trial of multivitamin supplementation for age-related lens opacities: clinical trial of nutritional supplements and age-related cataract report No. 3. Ophthalmology. 2008;115(4):599-607, e1.
PubMed   |  Link to Article
Christen  WG, Glynn  RJ, Manson  JE,  et al.  Effects of multivitamin supplement on cataract and age-related macular degeneration in a randomized trial of male physicians. Ophthalmology. 2014;121(2):525-534.
PubMed   |  Link to Article
Lippman  SM, Klein  EA, Goodman  PJ,  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(1):39-51.
PubMed   |  Link to Article
Lippman  SM, Goodman  PJ, Klein  EA,  et al.  Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Natl Cancer Inst. 2005;97(2):94-102.
PubMed   |  Link to Article
Klein  EA, Thompson  IM  Jr, Tangen  CM,  et al.  Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-1556.
PubMed   |  Link to Article
Packer  L.  Protective role of vitamin E in biological systems. Am J Clin Nutr. 1991;53(4)(suppl):1050S-1055S.
PubMed
Chow  CK, Reddy  K, Tappel  AL.  Effect of dietary vitamin E on the activities of the glutathione peroxidase system in rat tissues. J Nutr. 1973;103(4):618-624.
PubMed
Costagliola  C, Menzione  M.  Effect of vitamin E on the oxidative state of glutathione in plasma. Clin Physiol Biochem. 1990;8(3):140-143.
PubMed
Reed  DJ.  Glutathione: toxicological implications. Annu Rev Pharmacol Toxicol. 1990;30:603-631.
PubMed   |  Link to Article
Monsen  ER.  Dietary reference intakes for the antioxidant nutrients: vitamin C, vitamin E, selenium, and carotenoids. J Am Diet Assoc. 2000;100(6):637-640.
PubMed   |  Link to Article
Mares-Perlman  JA, Brady  WE, Klein  BE,  et al.  Diet and nuclear lens opacities. Am J Epidemiol. 1995;141(4):322-334.
PubMed   |  Link to Article
Institute of Medicine. Panel on Dietary Antioxidants and Related Compounds. Dietary Reference Intakes for Vitamin C, Vitamin E, and Carotenoids. Washingon, DC: National Academy Press; 2000.

Figures

Place holder to copy figure label and caption
Figure 1.
CONSORT Flow Diagram for the Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints (SEE) Study

Primary comparisons examine the main effects of the SELECT supplements (selenium vs no selenium, vitamin E vs no vitamin E) on occurrence of cataract.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Cumulative Incidence Rates of Cataract and Cataract Extraction by Randomized Selenium Assignment in the Selenium and Vitamin E Cancer Prevention Trial Eye Endpoints Study
Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Cumulative Incidence Rates of Cataract and Cataract Extraction by Randomized Vitamin E Assignment in the Selenium and Vitamin E Cancer Prevention Trial Eye Endpoints Study
Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1.  Baseline Characteristics by Randomized Groups in the Selenium and Vitamin E Cancer Prevention Trial Eye Endpoints Study
Table Graphic Jump LocationTable 2.  Confirmed Cases of Age-Related Cataract and Cataract Extraction According to Randomized Treatment Assignment in 4 Age Groups

References

Gerster  H.  Antioxidant vitamins in cataract prevention. Z Ernahrungswiss. 1989;28(1):56-75.
PubMed   |  Link to Article
Bunce  GE, Kinoshita  J, Horwitz  J.  Nutritional factors in cataract. Annu Rev Nutr. 1990;10:233-254.
PubMed   |  Link to Article
Varma  SD, Devamanoharan  PS, Morris  SM.  Prevention of cataracts by nutritional and metabolic antioxidants. Crit Rev Food Sci Nutr. 1995;35(1-2):111-129.
PubMed   |  Link to Article
Rasi  V, Costantini  S, Moramarco  A, Giordano  R, Giustolisi  R, Balacco Gabrieli  C.  Inorganic element concentrations in cataractous human lenses. Ann Ophthalmol. 1992;24(12):459-464.
PubMed
Yeum  KJ, Shang  FM, Schalch  WM, Russell  RM, Taylor  A.  Fat-soluble nutrient concentrations in different layers of human cataractous lens. Curr Eye Res. 1999;19(6):502-505.
PubMed   |  Link to Article
Varma  SD, Beachy  NA, Richards  RD.  Photoperoxidation of lens lipids: prevention by vitamin E. Photochem Photobiol. 1982;36(6):623-626.
PubMed   |  Link to Article
Libondi  T, Menzione  M, Auricchio  G.  In vitro effect of alpha-tocopherol on lysophosphatidylcholine-induced lens damage. Exp Eye Res. 1985;40(5):661-666.
PubMed   |  Link to Article
Karslioglu  I, Ertekin  MV, Koçer  I,  et al.  Protective role of intramuscularly administered vitamin E on the levels of lipid peroxidation and the activities of antioxidant enzymes in the lens of rats made cataractous with gamma-irradiation. Eur J Ophthalmol. 2004;14(6):478-485.
PubMed
Giblin  FJ.  Glutathione: a vital lens antioxidant. J Ocul Pharmacol Ther. 2000;16(2):121-135.
PubMed   |  Link to Article
Yung  LM, Leung  FP, Yao  X, Chen  ZY, Huang  Y.  Reactive oxygen species in vascular wall. Cardiovasc Hematol Disord Drug Targets. 2006;6(1):1-19.
PubMed   |  Link to Article
Arthur  JR.  The glutathione peroxidases. Cell Mol Life Sci. 2000;57(13-14):1825-1835.
PubMed
Patching  SG, Gardiner  PH.  Recent developments in selenium metabolism and chemical speciation: a review. J Trace Elem Med Biol. 1999;13(4):193-214.
PubMed   |  Link to Article
Alfthan  G, Aro  A, Arvilommi  H, Huttunen  JK.  Selenium metabolism and platelet glutathione peroxidase activity in healthy Finnish men: effects of selenium yeast, selenite, and selenate. Am J Clin Nutr. 1991;53(1):120-125.
PubMed
Nève  J.  Human selenium supplementation as assessed by changes in blood selenium concentration and glutathione peroxidase activity. J Trace Elem Med Biol. 1995;9(2):65-73.
PubMed   |  Link to Article
Levander  OA, Alfthan  G, Arvilommi  H,  et al.  Bioavailability of selenium to Finnish men as assessed by platelet glutathione peroxidase activity and other blood parameters. Am J Clin Nutr. 1983;37(6):887-897.
PubMed
Zhu  X, Guo  K, Lu  Y.  Selenium effectively inhibits 1,2-dihydroxynaphthalene-induced apoptosis in human lens epithelial cells through activation of PI3-K/Akt pathway. Mol Vis. 2011;17:2019-2027.
PubMed
Knekt  P, Heliövaara  M, Rissanen  A, Aromaa  A, Aaran  RK.  Serum antioxidant vitamins and risk of cataract. BMJ. 1992;305(6866):1392-1394.
PubMed   |  Link to Article
Jacques  PF, Chylack  LT  Jr, McGandy  RB, Hartz  SC.  Antioxidant status in persons with and without senile cataract. Arch Ophthalmol. 1988;106(3):337-340.
PubMed   |  Link to Article
Jacques  PF, Hartz  SC, Chylack  LT  Jr, McGandy  RB, Sadowski  JA.  Nutritional status in persons with and without senile cataract: blood vitamin and mineral levels. Am J Clin Nutr. 1988;48(1):152-158.
PubMed
Chiu  CJ, Taylor  A.  Nutritional antioxidants and age-related cataract and maculopathy. Exp Eye Res. 2007;84(2):229-245.
PubMed   |  Link to Article
Karaküçük  S, Ertugrul Mirza  G, Faruk Ekinciler  O, Saraymen  R, Karaküçük  I, Ustdal  M.  Selenium concentrations in serum, lens and aqueous humour of patients with senile cataract. Acta Ophthalmol Scand. 1995;73(4):329-332.
PubMed   |  Link to Article
Teikari  JM, Rautalahti  M, Haukka  J,  et al.  Incidence of cataract operations in Finnish male smokers unaffected by alpha tocopherol or beta carotene supplements. J Epidemiol Community Health. 1998;52(7):468-472.
PubMed   |  Link to Article
Sperduto  RD, Hu  TS, Milton  RC,  et al.  The Linxian cataract studies: two nutrition intervention trials. Arch Ophthalmol. 1993;111(9):1246-1253.
PubMed   |  Link to Article
Age-Related Eye Disease Study Research Group.  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. Arch Ophthalmol. 2001;119(10):1439-1452.
PubMed   |  Link to Article
Chylack  LT  Jr, Brown  NP, Bron  A,  et al.  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. Ophthalmic Epidemiol. 2002;9(1):49-80.
PubMed   |  Link to Article
McNeil  JJ, Robman  L, Tikellis  G, Sinclair  MI, McCarty  CA, Taylor  HR.  Vitamin E supplementation and cataract: randomized controlled trial. Ophthalmology. 2004;111(1):75-84.
PubMed   |  Link to Article
Christen  WG, Glynn  RJ, Chew  EY, Buring  JE.  Vitamin E and age-related cataract in a randomized trial of women. Ophthalmology. 2008;115(5):822-829, e1.
PubMed   |  Link to Article
Christen  WG, Glynn  RJ, Sesso  HD,  et al.  Age-related cataract in a randomized trial of vitamins E and C in men. Arch Ophthalmol. 2010;128(11):1397-1405.
PubMed   |  Link to Article
Maraini  G, Williams  SL, Sperduto  RD,  et al; Clinical Trial of Nutritional Supplements and Age-Related Cataract Study Group.  A randomized, double-masked, placebo-controlled clinical trial of multivitamin supplementation for age-related lens opacities: clinical trial of nutritional supplements and age-related cataract report No. 3. Ophthalmology. 2008;115(4):599-607, e1.
PubMed   |  Link to Article
Christen  WG, Glynn  RJ, Manson  JE,  et al.  Effects of multivitamin supplement on cataract and age-related macular degeneration in a randomized trial of male physicians. Ophthalmology. 2014;121(2):525-534.
PubMed   |  Link to Article
Lippman  SM, Klein  EA, Goodman  PJ,  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(1):39-51.
PubMed   |  Link to Article
Lippman  SM, Goodman  PJ, Klein  EA,  et al.  Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Natl Cancer Inst. 2005;97(2):94-102.
PubMed   |  Link to Article
Klein  EA, Thompson  IM  Jr, Tangen  CM,  et al.  Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-1556.
PubMed   |  Link to Article
Packer  L.  Protective role of vitamin E in biological systems. Am J Clin Nutr. 1991;53(4)(suppl):1050S-1055S.
PubMed
Chow  CK, Reddy  K, Tappel  AL.  Effect of dietary vitamin E on the activities of the glutathione peroxidase system in rat tissues. J Nutr. 1973;103(4):618-624.
PubMed
Costagliola  C, Menzione  M.  Effect of vitamin E on the oxidative state of glutathione in plasma. Clin Physiol Biochem. 1990;8(3):140-143.
PubMed
Reed  DJ.  Glutathione: toxicological implications. Annu Rev Pharmacol Toxicol. 1990;30:603-631.
PubMed   |  Link to Article
Monsen  ER.  Dietary reference intakes for the antioxidant nutrients: vitamin C, vitamin E, selenium, and carotenoids. J Am Diet Assoc. 2000;100(6):637-640.
PubMed   |  Link to Article
Mares-Perlman  JA, Brady  WE, Klein  BE,  et al.  Diet and nuclear lens opacities. Am J Epidemiol. 1995;141(4):322-334.
PubMed   |  Link to Article
Institute of Medicine. Panel on Dietary Antioxidants and Related Compounds. Dietary Reference Intakes for Vitamin C, Vitamin E, and Carotenoids. Washingon, DC: National Academy Press; 2000.

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Supplement.

eTable. Relative Rates of Age-Related Cataract by Randomized Treatment Assignment Within Subgroups in the SELECT Eye Endpoints (SEE) Study.

Supplemental Content

Some tools below are only available to our subscribers or users with an online account.

1,475 Views
6 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs
JAMAevidence.com

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed
An Illustration of Bias and Random Error

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed
An Illustration of Bias and Random Error