Daily supplements could reduce AMD risk

November 1, 2007

Randomized data from a large cohort of women with cardiovascular disease or at a high risk of it indicate that seven years of daily supplementation with folic acid, vitamin B6, and vitamin B12 may reduce the risk of age-related macular degeneration (AMD), according to William G. Christen, ScD, PhD.

Speaking at the annual meeting of the Association for Research in Vision and Ophthalmology in Fort Lauderdale, Florida, US, earlier this year, he presented results from more than 5,000 women. The study showed that the combination of folic acid, vitamin B6, and vitamin B12 reduced the risk of confirmed AMD by 34% and the risk of visually significant AMD by 41% over 7.3 years of treatment and follow-up.

Dr Christen presented AMD findings from the Women's Antioxidant Folic Acid Cardiovascular Study (WAFACS). This was a double-blind, placebo-controlled, 2 x 2 x 2 x 2 factorial trial of folic acid, vitamin B6, and vitamin B12 conducted among women already randomly assigned to receive vitamin C, vitamin E and beta-carotene.

The intervention that was tested was a combination of folic acid (2.5 mg daily), vitamin B6 (50 mg daily) and vitamin B12 (1 mg daily).

How is cardiovascular risk linked with AMD?

The study was conducted because there has been speculation that AMD and cardiovascular disease share similar mechanisms and risk factors, one of which is the amino acid homocysteine, Dr Christen said. Homocysteine is derived from the metabolism of methionine, an essential amino acid derivative from dietary protein.

According to Dr Christen, inadequate intake of folic acid and other B vitamins can lead to increased concentrations of homocysteine in the blood. Experimental studies have shown that hyperhomocysteinaemia can induce endothelial dysfunction, impair vascular reactivity, and promote inflammatory processes leading to atherosclerosis. All of these factors are believed to be involved in the pathophysiology of AMD. It has also been clearly demonstrated that supplementation with folic acid and other B vitamins can significantly reduce homocysteine levels in the blood.

Both cross-sectional and case-control studies have reported an association between plasma homocysteine and AMD.

The trial

The original trial, of which the folic acid study was a part, began in late 1994 when 11,280 women were enrolled in a run-in; baseline blood samples were collected from 72% of the group. After successful completion of the run-in period, 8,171 of the women were randomly assigned to the antioxidant arms of the trial. In April 1998, three years after this randomization, 5,442 participants were further randomly assigned into the folic acid, vitamin B6, and vitamin B12 portion of the study. The WAFACS study began several months after folic acid fortification of cereal-grain products was fully implemented in the United States.

The average age of women in WAFACS at baseline was 62.6 years. About 86% of the women in the active treatment and placebo groups reported hypertension at baseline, about 78% reported hyperlipidaemia, and about 21% reported diabetes. In both groups, 64% had preexisting cardiovascular disease. The mean body mass index ([BMI], kg/m2 ) was 30.6 in the active treatment group and 30.7 in the placebo group.