About 12% reported being current smokers, about 33% reported daily alcohol use, 22% to 23% said they used multivitamins, and
62% in both groups said they had used aspirin within the past month.
Follow-up blood samples were collected from 300 participants in early 2005, and the women completed taking their pills in
July of that year. Follow-up was completed in July 2006.
Over the course of the trial, the women completed annual questionnaires in which they reported their compliance with study
medication and the occurrence of any relevant study endpoints, such as the development of AMD. When AMD was reported, investigators
sought consent to review medical records and sent an AMD questionnaire to the diagnosing eye doctor.
"What we sought to do was to determine the date of initial diagnosis of AMD, the date when visual acuity was first noted to
be 20/30 or worse, the retinal signs of AMD that were present when acuity was first 20/30 or worse, and whether there were
other ocular abnormalities that would explain the visual acuity loss, and if so we asked the eye doctor to give us his or
her impression as to whether or not the AMD was severe enough to reduce vision to 20/30 or worse," Dr Christen said.
Number of AMD cases was lower in those receiving supplements
Analysis of results from the WAFACS study showed that cases of AMD occurred in both the active and placebo groups but at higher
rates among the latter.
"Over an average of 7.3 years of treatment and follow-up, a total of 137 cases of confirmed AMD were documented, including
70 cases of visually significant AMD," Dr Christen said.
Data on the retinal signs indicative of visually significant AMD showed that about 70% of the cases were characterized by
a combination of drusen and retinal pigment epithelium changes. However, these cases still represented a relatively early
stage of AMD development, Dr Christen added.
Investigators were able to document 55 confirmed cases of AMD in the active treatment group and 82 in the placebo arm of the
WAFACS. The relative risk (RR) was 0.66 (95% CI, 0.47 to 0.93). Twenty-six cases of visually significant AMD occurred in the
active group and 44 occurred in the placebo group (RR 0.59; 95% CI, 0.36 to 0.95).
The rates of confirmed AMD cases in the active and placebo groups began to diverge after about two years of treatment and
follow-up and remained separated for the duration of the trial. For visually significant AMD, the divergence began later,
at about four years.
Digging deeper to find the answer
Investigators also analysed the impact of baseline characteristics such as age, cigarette smoking, alcohol use, BMI, and medical
"We found no evidence that the effect of folic acid and other B vitamins on visually significant AMD, or on confirmed AMD
for that matter, was modified by any of the risk factors at baseline," Dr Christen said.
He also presented results of a blood sub-study conducted to evaluate the effect of folic acid fortification and folic acid
supplementation on homocysteine levels. At the beginning of the WAFACS trial, the folic acid levels in a sample of 300 participants
were a mean of 9.2 ng/ml in the placebo group and 9 ng/ml in the active treatment group.
By the end of the study, folic acid levels in the placebo group had increased to 16.4 ng/ml (p<0.001). This change presumably
reflects the effect of folic acid fortification of food in the United States, Dr Christen said. In the active treatment arm,
the folic acid level more than quadrupled to 39.6 ng/ml (p<0.001).
Homocysteine levels in this sample did not change between baseline and follow-up in the placebo group despite the fact that
folic acid levels had increased significantly; the level remained at 12.3 μmol/l. In the active group, the level declined
from 12.2 to 10 μmol/l (p < 0.001), about 18%.
"Additional studies will be required to determine to what extent, if any, the beneficial effect of folic acid and other B
vitamins on AMD is mediated by their homocysteine-lowering effect," Dr Christen concluded.
William G. Christen, ScD, PhD is associate professor of medicine at Harvard Medical School, and associate epidemiologist at Brigham and Women's Hospital,
Boston, US. He may be reached by E-mail: email@example.com
The study was supported by grants from the National Heart, Lung and Blood Institute at the National Eye Institute in the US.
Dr Christen reported no commercial relationships.