BOSTON -- Supplemental beta carotene over 12 years had no beneficial effect on the occurrence rate of age-related maculopathy, found researchers here.
BOSTON, March 14 -- Supplemental beta carotene over 12 years had no beneficial effect on the occurrence rate of age-related maculopathy, found researchers here.
This finding emerged from the Physicians' Health Study 1, a randomized, double-blind, placebo-controlled trial with 22,071 U.S. male physicians, ages 40 to 84, reported William Christen, Sc.D., of Harvard's Brigham and Women's Hospital, and colleagues, in the March issue of the Archives of Ophthalmology.
The study had tested beta carotene and low-dose aspirin in this group, and found no benefit and no harm after 12 years' use of beta carotene on cancer or cardiovascular disease as the end points, Dr. Christen said.
The current age-related maculopathy study used the randomized beta carotene component of the study. Participants were randomly assigned to receive 50 mg of beta carotene every other day or placebo. Maculopathy was defined as a reduction in best-corrected vision to 20/30 or worse.
The investigators found that after 12 years of treatment and follow-up, there were 162 cases of age-related macular degeneration in the beta carotene group versus 179 cases in the placebo arm (relative risk 0.96, 95% CI, 0.78-1.20).
The results were similar for the secondary endpoints of age-related maculopathy with or without vision loss, 275 versus 274 cases (RR 1.01, CI 0.86-1.20) and for advanced maculopathy, 63 versus 66 cases (RR 0.97, CI, 0.69-1.37).
For all three endpoints, the relative risks did not vary significantly among the four age groups (interaction P> 0.7 for all).
There were no significant effects of supplementation on any of the end points after excluding cases diagnosed during the first two years of follow-up, the researchers reported.
Men in the beta carotene group had a nonsignificant 4% lower risk of visually significant age-related maculopathy. The 95% CI around this estimate excluded a beneficial effect of 25% or greater or a harmful effect of 20% or greater. The relative risk estimates for the secondary endpoints (with or without visions loss or advanced disease) were near the null value of 1.0, the researchers said.
An earlier study, the Age-Related Eye Disease Study (AREDS), found that high-dose antioxidant supplementation could mitigate the progression of advanced maculopathy in patients at high risk, the researchers said.
Although beta carotene was included in the AREDS trial, the antioxidant was tested in combination with other agents, including ascorbic acid and vitamin E, so that the role of beta carotene could not be determined.
The results of the current study, Dr. Christen said, suggest that the reduction in the maculopathy progression observed for the antioxidant combination in the AREDS formulation is unlikely to reflect an important independent beneficial effect for beta carotene, and removal of the supplement should have no material effect on the efficacy of the supplement.
Nevertheless, the researchers said, a possible indirect effect of beta carotene in the AREDS formulation, mediated through interaction with other trial ingredients, cannot be excluded.
In discussing the study's limitations, the researchers said it was unlikely that an inadequate dosage explained the findings, since plasma beta carotene levels increased about four-fold.
It also seemed unlikely that the 12-year duration of treatment was insufficient, nor does poor compliance with the assigned treatment seem a likely explanation. In addition, they said, confounding was not likely, since the trial was large and baseline characteristics were similar in the placebo and treatment groups.
In summary, Dr. Christen and his colleagues said, despite its common occurrence, there are no generally available treatment options, so that identification of prevention measures is of particular clinical and public health importance. "These findings, together with forthcoming data from other completed and on-going trials, will complement the findings in the AREDS by clarifying the effect of individual antioxidant supplements and other nutritional combinations."
These studies should help ensure rational clinical and public health recommendations for the prevention of age-related macular degeneration, they concluded.