Daniel Epshtein, OD, FAAO, and Priya Vakharia, MD, FASRS, discussed emerging evidence for B-vitamin supplementation in age-related macular degeneration (AMD) on this episode Ready, Set, Retina.
Dr. Vakharia is a retina specialist at Retina Vitreous Associates of Florida and assistant professor at the University of South Florida.
“For a lot of these patients, they've seen their family members lose their vision, and they are hopeful for new therapies or vitamins that could help prevent progression.”
B-vitamin supplementation in AMD fast facts
- Age-related macular degeneration is classified as early, intermediate, or late based on drusen size and characteristics; only intermediate AMD has an evidence-based nutritional treatment today.
- The original AREDS formula reduced progression to advanced AMD by about 25% in patients with intermediate disease.1
- Neither AREDS nor AREDS2 has shown benefit for early AMD, a stage that affects far more patients and currently has no approved treatment.
- PreserVision AREDS3, a new Bausch + Lomb product, adds a B-complex vitamin blend and lowers zinc to reduce GI upset—it has not yet been tested in a dedicated National Eye Institute trial.
- The evidence behind adding B vitamins comes primarily from cardiovascular and observational population studies, not randomized eye-specific trials with OCT or fundus photography as endpoints.
The trial that wasn't supposed to be about eyes
WAFACS wasn't designed to study eyes at all. The Women's Antioxidant and Folic Acid Cardiovascular Study randomized 5,442 women with cardiovascular disease or major cardiac risk factors to a daily folic acid, B6, and B12 combination or placebo, purely to test heart disease prevention—AMD got tracked almost as an afterthought.2
After 7.3 years of daily supplementation, the results on AMD were hard to ignore:2
- 34% lower risk of confirmed AMD vs. placebo.
- 41% lower risk of visually significant AMD vs. placebo.
- Results held across 7.3 years of average follow-up, among women with no eye disease at baseline.
Unlike the AREDS antioxidant formula, which only works once drusen accumulates to a significant burden, this is the first randomized evidence that B vitamins might lower the risk of AMD happening in the first place. The proposed mechanism runs through homocysteine, an amino acid that damages blood vessels when it builds up and that B vitamins help clear.
Additional evidence linking B vitamins potential AMD risk reduction
Population data back up the connection: In the observational Blue Mountains Eye Study, vitamin B12 deficiency was linked to 58% higher odds of early AMD and more than double the odds of late AMD, while participants who reported taking a B12 supplement had 47% lower odds of any AMD.3
Unlike WAFACS, this wasn't randomized—it's an association, not proof the supplement caused the difference—and Dr. Vakharia is upfront that the broader evidence is still hypothesis-generating.
That distinction matters for how the formula gets used. AREDS2 remains standard for intermediate AMD, where the risk reduction from the original AREDS trial is well established,1 while Preservision AREDS3's B-vitamin blend may additionally target early AMD—a population with no treatment option. In these patients, Dr. Vakharia suggests that the use of a B complex vitamin is low risk and potentially beneficial.
“I don't know yet if PreserVision AREDS3 will help prevent progression, but I consider it—or at least consider a B complex vitamin.”
Key takeaways
- WAFACS, a randomized cardiovascular trial, found a 34% lower risk of confirmed AMD and a 41% lower risk of visually significant AMD in women taking daily folic acid, B6, and B12 compared with placebo.2
- The observational Blue Mountains Eye Study found vitamin B12 deficiency linked to higher odds of early and late AMD, and B12 supplement users had 47% lower odds of any AMD, corroborating WAFACS with population-level (not randomized) data.3
- The evidence for B vitamins and AMD comes primarily from cardiovascular and population cohorts, not eye-specific trials; Dr. Vakharia calls it compelling but still hypothesis-generating.
- AREDS2 remains standard of care for intermediate AMD, where the original AREDS trial's 25% risk reduction is well established; B complex vitamins may help with early AMD, a stage with no other treatment option.
- Because B vitamins are water-soluble, the downside risk of recommending them may be low although further evidence is needed... PreserVision AREDS3 is on shelves, ahead of any dedicated NEI trial.
