Vitamins, Folic Acid Reduce AMD Risk in Women

Medical News: Ophthalmology

By Michael Smith, North American Correspondent, MedPage Today
Published: February 23, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

BOSTON, Feb. 23 -- Daily B-vitamin and folic-acid supplements reduced the risk of age-related macular degeneration (AMD) in women, researchers here said. Action Points
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Explain to interested patients that a link has been proposed between blood levels of homocysteine and age-related macular degeneration, opening the possibility that lowering those levels might reduce the risk of the disease.

Note that this study, in which folic acid and two B vitamins were used to reduce homocysteine levels in women, showed a marked reduction in the risk of the disease.
In a randomized clinical trial, taking vitamin B6 and B12 (pyridoxine hydrochloride and cyanocobalamin) along with folic acid reduced the risk of the condition by 34%, according to William Christen, Sc.D., of Brigham and Women's Hospital, and colleagues.

The supplements reduced the risk of visually significant macular degeneration by 41%, they reported in the Feb. 23 issue of Archives of Internal Medicine.

The findings are "the strongest evidence to date in support of a possible beneficial effect" in prevention of the condition, the researchers said.

And -- because the findings apply to the early stages of disease -- they may be the first identified way, other than not smoking, to reduce the risk in people otherwise at average risk, the researchers said.

The findings come from the Women's Antioxidant and Folic Acid Cardiovascular Study, a randomized, double-blind, placebo-controlled trial whose main goal was to see if the combination treatment could prevent cardiovascular events among women at high risk for cardiovascular disease.

Participants were randomly assigned to get a daily combination of 2.5 milligrams of folic acid, 50 milligrams of vitamin B6, and one milligram of vitamin B12, or matching placebos.

The study included 5,442 female healthcare professionals 40 or older either with pre-existing cardiovascular disease or at least three cardiovascular disease risk factors.

At baseline, 5,205 of these participants did not have a diagnosis of age-related macular degeneration and were included in this analysis.

The main outcome measures were any form of age-related macular degeneration and visually significant disease, defined as confirmed incident age-related macular degeneration leading to visual acuity of 20/30 or worse.

After an average of 7.3 years of treatment and follow-up, the researchers found:

55 cases of age-related macular degeneration in the treatment group and 82 in the placebo group, for a relative risk of 0.66, with a 95% confidence interval from 0.47 to 0.93, which was significant at P=0.02.
26 cases of visually significant degeneration in the treatment group and 44 in the placebo group, for a relative risk of 0.59 with a 95% confidence interval from 0.36 to 0.95, which was significant at P=0.03.

The benefit of treatment "began to emerge at approximately two years of follow-up and persisted throughout the trial," the researchers said.

Although women in the treatment group in a substudy had a significant reduction (at P<0.001) in their geometric mean plasma homocysteine levels (18.5%, 0.31mg/L), it is still not conclusive evidence that lowering levels of the protein caused the reduction in AMD risk, Dr. Christen and colleagues said.

Other treatment mechanisms are possible, they said, including a direct antioxidant effect on the choroidal vasculature.

They also noted that "our findings for AMD are in sharp contrast to the null findings for CVD observed in other completed trials to lower homocysteine levels in persons with pre-existing vascular disease, despite substantial lowering of homocysteine concentrations by study treatment in those trials."

The researchers concluded that their findings could be due to chance and need confirmation, but "it may be worthwhile to consider whether the discordant findings for AMD and CVD reflect important differences between the choroidal and systemic vasculature with respect to responsiveness to the lowering of homocysteine levels."

The study was supported by the National Heart, Lung, and Blood Institute and the National Eye Institute. Vitamin E and its placebo were provided by Cognis Corp. and all other agents and their placebos were provided by BASF Corp.
Dr. Christen reported research grants from DSM Nutritional Products, Inc, (Roche).

Primary source: Archives of Internal Medicine
Source reference:
Christen WG, et al "Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: The Women's Antioxidant and Folic Acid Cardiovascular Study" Arch Intern Med 2009; 169(4): 335-341.
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