Understanding the Results of AREDS2

2nd Age-Related Eye Disease Study (AREDS2)

Results of the second AREDS trial (AREDS2) were released in early May (1). The bottom line? Consider taking the original AREDS formula with beta-carotene replaced by lutein and zeaxanthin if you have at least intermediate AMD.

AREDS2 had a complex study design. All participants were randomly assigned to one of four groups: placebo (the control group), lutein (10 mg) plus zeaxanthin (2 mg), omega-3 fatty acids (1000 mg), or both.

Everyone in the trial was also offered the original AREDS formula (vitamins C and E, beta-carotene, zinc and copper). Many opted to take the original supplement, while others agreed to take modified formulas with reduced zinc and/or no beta-carotene.

The main goal of the study was to see whether adding lutein + zeaxanthin or omega-3 fatty acids to an AREDS formula would be more effective in reducing the risk to advanced AMD than taking the AREDS formula alone.

Compared to taking only the AREDS formula, neither the added omega-3 nor lutein/zeaxanthin met the additional 25% decrease in risk that was required to show effectiveness.

However, there were other important sub-group findings – not widely covered by the media – that may well have influenced the main outcome in the lutein + zeaxanthin groups.

Lutein and Zeaxanthin May Be of Benefit

High dose beta-carotene appeared to interfere with the absorption of lutein/zeaxanthin, as evidenced by lower blood levels of lutein/zeaxanthin in those getting the original formula with beta-carotene. In fact, when beta-carotene was removed from the formula, the researchers did find evidence that lutein + zeaxanthin can slow progression to advanced AMD.

Those taking lutein + zeaxanthin and no beta-carotene had an 18% lower risk compared to people getting beta-carotene (and no lutein + zeaxanthin).

In addition, the lutein/zeaxanthin supplements made a real difference for those with the lowest dietary intake of these carotenoids. A 26% reduction in risk of progression was seen for those with the poorest dietary intake who received lutein and zeaxanthin.

The investigators noted that overall, AREDS2 participants tended to have diets richer in lutein and zeaxanthin than the general population. That’s important because a substantial portion of Americans typically consume less than 1-2 mg of these carotenoids daily.

According to the investigators, it’s possible that a greater benefit would have been seen for lutein/zeaxanthin if the diets of the AREDS2 patients had been more representative of the general population.

What About Zinc and Beta Carotene?

Another goal of the study was to assess the effects of lowering the zinc dose from the original 80 mg to 25 mg, and eliminating beta-carotene. Neither of these changes made a significant difference in the effectiveness of the formula.

The higher dose of zinc, however, showed a favorable trend toward better protection, and there was no difference observed between the two zinc doses in terms of safety. Therefore the research group recommends the higher dose of zinc, while noting that the zinc results were not definitive.

The researchers also recommend substituting lutein and zeaxanthin for beta-carotene in the original AREDS formula for safety reasons. More cases of lung cancer were seen in participants who took a beta carotene-containing formula than in those who did not, and most of those who developed lung cancer were former smokers.

AREDS Benefits Are Long-Lasting

In a recently published follow-up study of the original AREDS trial, researchers found that the effects of taking the AREDS supplement are long- lasting (2).

After the original trial ended, participants were followed for another 5 years. At the end of that period, those who had taken the AREDS formula were 25-30% less likely to develop advanced AMD.

Considering the findings of this follow-up study and of AREDS2, there’s every reason to be confident that the AREDS formula (with lutein and zeaxanthin replacing beta carotene) will provide at least similar protection against the progression of AMD.

Cataract

AREDS2 also asked whether adding lutein/zeaxanthin or omega-3s to the original AREDS formula would impact the need for cataract surgery (3). No statistically significant overall effect was seen.

However, again, participants with the poorest intake of dietary lutein and zeaxanthin did benefit by getting supplements of these carotenoids. This group was 32% less likely to progress to a level of cataract requiring cataract surgery. A 36% reduction in the development of any severe cataract was seen as well.

Take Home Message?

While AREDS2 was a complicated trial, the overall message is simple: If you have at least intermediate AMD, discuss taking the AREDS formula (containing lutein + zeaxanthin) with your doctor. This is especially important if you have AMD or cataract and don’t include enough lutein and zeaxanthin-rich leafy greens such as kale, collards and spinach in your diet.

Omega-3s: More Research Needed

AREDS2 found that the omega-3s taken with the AREDS formula did not provide further benefit for those with intermediate to advanced AMD. However, that does not rule out a possible benefit for people with early stage AMD or who are at risk for the disease.

One population health study (4) with over 38,000 women who were free of AMD at the study’s start, reports that regular intake of the omega-3s over a 10-year period significantly lowered the risk of developing AMD. While these findings suggest that the omega-3s could be helpful in primary prevention of AMD, more research is needed to understand what role the omega-3s may play in maintaining visual health.

References

1. The AREDS2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration. JAMA Ophthalmol Epub ahead of print, May 5, 2013.
2. Chew EY et al. Long-term effects of vitamins C and E, B-carotene, and zinc on age-related macular degeneration Ophthalmology Epub ahead of print, April 11, 2013.
3. The AREDS2 Research Group.
4. Christen WG, et al. Dietary omega-3 fatty acid and fish intake and incident Age-Related Macular Degeneration in women. Arch Ophthalmol 129:921-29, 2011.