Carotenoid-Rich Diet May Protect Against Advanced Eye Disease

Diana Phillips

October 14, 2015

High intake of dietary components lutein and zeaxanthin is associated with a long-term reduced risk for advanced age-related macular degeneration (AMD), new research shows.

The findings, published online October 8 in JAMA Ophthalmology, add to the evidence base suggesting carotenoids exert a protective effect against the progressive eye disease, according to Juan Wu, MS, from the Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, and colleagues.

To date, evidence from epidemiologic studies and clinical trials on the relationship between intakes of lutein and zeaxanthin and AMD has been inconsistent, "despite compelling biological plausibility," and the roles of other carotenoids are less thoroughly investigated, the authors write. "The recently concluded Age-Related Eye Disease Study 2 trial was unable to confidently demonstrate protective effects of lutein/zeaxanthin, and whether lutein/zeaxanthin may protect against early AMD also remains unknown."

For the current study, the investigators aimed to further explore the suggestive inverse association of lutein/zeaxanthin with advanced AMD they reported in 2008, using data from the prospective Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). "With an additional decade of follow-up and the occurrence of a large number of additional incident AMD cases, we aimed to provide more detailed insights into the roles of carotenoids in the development of AMD," they write.

The study population, comprising 63,443 women and 38,603 men, was followed from 1984 until May 31, 2010, in the NHS and from 1986 until January 31, 2010, in the HPFS. All participants were aged 50 years or older and were free of diagnosed AMD, diabetes mellitus, cardiovascular disease, and cancer (except nonmelanoma skin cancer) at baseline.

During 26 years of follow-up for participants in the NHS and 24 years for those in the HPFS, the researchers found 1361 incident intermediate and 1118 advanced cases of AMD, more than 96% of which were neovascular AMD. The age at AMD onset was a median of 73 years in women and 76 years in men.

The researchers assessed carotenoid intake based on dietary self-report, from which they calculated predicted plasma carotenoid scores.

When the researchers compared extreme quintiles of predicted plasma lutein/zeaxanthin score, they found an approximately 40% reduced risk for advanced AMD (relative risk = 0.59; 95% confidence interval, 0.48 - 0.73; P for trend < .001).

Similarly, "[p]redicted plasma carotenoid scores for other carotenoids, including β-cryptoxanthin, α-carotene, and β-carotene were associated with a 25% to 35% lower risk of advanced AMD," the authors write.

The investigators observed no association between the outcome of intermediate AMD and any of the predicted plasma carotenoid scores, suggesting intake of carotenoids has an effect on AMD progression, rather than initiation.

"Lutein and zeaxanthin form macular pigments that may protect against AMD by reducing oxidative stress, absorbing blue light, and stabilizing cell membranes," the authors explain.

A significant correlation between serum lutein and zeaxanthin and macular pigment optical density has been observed in cross-sectional and experimental studies, and evidence also suggests an association between genetic variants related to lutein and zeaxanthin metabolism and macular pigment optical density or AMD, the authors write. "Therefore, multiple independent lines of evidence point to a protective role of lutein and zeaxanthin in the development of advanced AMD," they state.

The researchers hypothesize that the potent antioxidant properties of carotenoids may reduce systemic oxidative stress that indirectly influences the macula.

"Because other carotenoids may also have a protective role, a public health strategy of increasing the consumption of a wide variety of fruits and vegetables rich in carotenoids could be most beneficial and is compatible with current dietary guidelines," the authors conclude.

"There are some advantages of this prospective cohort study, since it is a longer-term study. However, weaknesses include the assessment of AMD based on self-reporting on a questionnaire," Abdhish Bhavsar, MD, a clinical spokesperson for the American Academy of Ophthalmology, told Medscape Medical News. Dr Bhavsar is the director of clinical research and a practicing ophthalmologist at the Retina Center in Minneapolis, Minnesota. Because the investigators performed chart reviews based on the self-reported information, under- or overreporting is a possibility, he said. "In addition, cohort studies are unable to determine cause and effect very well."

On the basis of this study and other available evidence, however, "there is scientific plausibility and some evidence with this cohort study to suggest that lutein/zeaxanthin and carotenoids in the diet at higher levels may be of benefit in reducing the risk of AMD," Dr. Bhavsar said.

This study was supported by grants from the National Institutes of Health. The study authors and Dr. Bhavsar have disclosed no relevant financial relationships.

JAMA Ophthalmol. Published online October 8, 2015. Full text

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