In this large population of female health professionals, significant inverse trends with risk of cataract were observed for dietary intake of lutein/zeaxanthin and vitamin E. Comparing women in extreme quintiles, women with high intake of lutein/zeaxanthin had an 18% lower risk of cataract in multivariate analysis (P, test for trend = 0.045). High intake of vitamin E from food and supplements was associated with a 14% lower risk of cataract (P, test for trend = 0.03). The inverse associations for lutein/zeaxanthin and vitamin E from food and supplements persisted in models that mutually adjusted for intake of several other carotenoids and vitamin C.
The prospective design of this study precluded the possibility that participant reports of nutrient intake at baseline were associated with subsequent cataract status. However, random or nondifferential misclassification of dietary intake was likely and would tend to underestimate any association of diet with risk of cataract. Changes in dietary behavior during follow-up seem unlikely to be differential with respect to the cataract endpoint, and thus would also attenuate the true associations. Random misclassification of the cataract endpoint was reduced by the use of medical records to confirm the participant reports and by the use of strict diagnostic criteria. To control for possible surveillance bias, we included a term for the baseline report of an eye exam in the last two years in multivariate analyses. Finally, we controlled for a number of measured confounders (), but other potential confounders which were either unmeasured or unknown may have contributed to the findings.
There have been three other prospective studies that examined the relationship of dietary intake of lutein and risk of cataract. In the Nurses’ Health Study of 77,466 female nurses, women in the top 10% of lutein/zeaxanthin intake, compared to those in the bottom quintile, had a 22% lower risk of cataract extraction (RR, 0.78; 95% CI, 0.63-0.95; P, test for trend = 0.04) during 12 years of follow-up (28
). In another report from that cohort, based on a small subsample of 408 participants, there was no association between intake of lutein/zeaxanthin and 5-year change in nuclear density as measured by analysis of digital images (32
). In a second study, data from the Health Professionals Study of 36,644 male health professionals showed that men in the highest quintile of lutein/zeaxanthin intake, compared to those in the lowest, had a 19% lower risk of cataract extraction (RR, 0.81; 95% CI, 0.65-1.01; P, test for trend = 0.03) during 8 years of follow-up (27
). A third study, based on data from 1,354 men and women participating in a nutrition substudy in the Beaver Dam Eye Study, showed that those in the highest quintile of intake of lutein/zeaxanthin in the distant past (10 years before baseline), compared to those in the lowest quintile, had a 50% decreased risk of incident nuclear opacity (OR, 0.5; 95% CI, 0.3-0.8; P, test for trend = 0.002) at 5 years of follow-up (29
). Our data from a large cohort of female health professionals indicate an approximate 20% decreased risk of cataract for those with high dietary intake of lutein/zeaxanthin, and thus appear most consistent with the findings for cataract extraction reported in the Nurses’ Health Study and Health Professionals Study (27
). Of note, lutein/zeaxanthin intake in the reference group in the WHS and the two other cohorts of health professionals (27
) appear markedly higher than the reference intake for lutein/zeaxanthin in the population-based sample from Beaver Dam (29
), which may at least partially explain the smaller risk reductions observed in the former.
Among the other carotenoids examined in our study, only beta-carotene from food and supplements showed a possible inverse relation with risk of cataract. Women in the highest, compared to the lowest, quintile of intake had a borderline significant (p=0.051) 13% reduced risk of cataract in multivariate analysis. However, the test for trend across quintiles was not significant in the multivariate model, or after adjustment for intake of other nutrients. These findings appear consistent with most earlier prospective studies which report a weak and statistically nonsignificant inverse trend between beta-carotene level in the diet or blood and risk of cataract (27
). More importantly, results of five randomized trials clearly indicate that supplemental use of beta-carotene (with or without other antioxidant supplements) for as long as 12 years has little impact on risks of cataract (7
We observed a significant inverse trend between vitamin E intake from food and supplements and risk of cataract in our population of women. This inverse trend persisted after adjustment for other nutrients and appeared to be due largely to a 14% reduced risk of cataract for women in the highest quintile of intake. Median intake of vitamin E for this group of women was 262.4 mg/day, a level of intake difficult to attain from food sources only. The reduction in risk appeared to reflect supplemental use of vitamin E rather than multivitamins. Seventy-one percent of women in the highest quintile of vitamin E intake reported using supplements of vitamin E at baseline, and adjustment for use of multivitamins had little impact on the RR estimate (RR comparing extreme quintiles of vitamin E intake, 0.86; 95% CI, 0.73-1.00; p-trend = 0.048). Results of other prospective studies have been mixed with some supporting an inverse association between dietary or serum vitamin E and cataract (32
) while others report no association (29
). Data from five randomized trials completed to date provide little evidence that use of vitamin E supplements, alone or in combination with other vitamin supplements, for treatment periods as long as 6.5 years has any material impact on cataract development and progression (8
). The final results for cataract during the 10 year treatment period for vitamin E in the WHS will be reported elsewhere.
Our data for vitamin C indicate a weak, and statistically nonsignificant, inverse association with risk of cataract. This finding appears to conflict with cross-sectional data presented in two recent reports from the Nurses’ Health Study (30
), but is consistent with the results of several other prospective studies (29
) including 5-year follow-up data in the Nurses’ Health Study subsample (32
). Furthermore, findings in three randomized trials indicate no major benefit for combined treatment with vitamin C and other antioxidants for treatment durations as long as 6.5 years (8
The hypothesis that antioxidant nutrients may protect against age-related damage to the human lens was derived from laboratory and animal studies, and has been generally supported by findings of observational epidemiologic studies in humans. However, the results of completed randomized trials testing vitamin E, vitamin C, or beta-carotene have been disappointing and ongoing trials will determine whether observable benefits on cataract can emerge with longer-term treatment with these antioxidant vitamins. In the meantime, the results of the present study add to the growing body of observational evidence to suggest a possible beneficial effect for lutein/zeaxanthin in delaying cataract formation. Lutein and zeaxanthin are the only carotenoids detected in the human lens (18
), and the presence of oxidation products of lutein and zeaxanthin in the lens (54
) further supports a functional role for xanthophylls in maintaining lens clarity.
In conclusion, these prospective data from a large cohort of female health professionals indicate that higher intakes of lutein/zeaxanthin and vitamin E are associated with decreased risks of cataract. While reliable data from randomized trials are accumulating for vitamin E and other antioxidant vitamins, randomized trial data for lutein/zeaxanthin are lacking. Such information will help to clarify the benefits of supplemental use of lutein/zeaxanthin, and provide the most reliable evidence on which to base public health recommendations for cataract prevention by vitamin supplementation.