The National Institutes of Health (NIH) Age-Related Eye Disease studies (AREDS and AREDS2) established that dietary supplements can slow the progression of age-related macular degeneration (AMD) a leading cause of blindness in older Americans. AREDS2, the later formula investigated by researchers, was initially found to have no extra benefit to AMD risk in a paper published in 2013 after a median follow-up of five years.  
 
However, in a new report, scientists analyzed a full 10 years of AREDS2 data, which suggested superiority of the later formula to the one used in the original AREDS study. The AREDS2 formula substituted lutein and zeaxanthin in place of beta-carotene due to concerns about the fact that beta-carotene increases the risk of lung cancer in current smokers. Further, the formula was more beneficial to eye health because of the substitution, as shown by a greater reduced risk of AMD progression, according to the authors. AMD is a degenerative disease of the retina, and the progressive death of retinal cells in the macula eventually leads to blindness. Treatment can slow or reverse vision loss, however, no cure for AMD exists.
 
The present study was funded by NIH and was published in JAMA Ophthalmology.
 
“Because beta-carotene increased the risk of lung cancer for current smokers in two NIH-supported studies, our goal with AREDS2 was to create an equally effective supplement formula that could be used by anyone, whether or not they smoke,” said Emily Chew, MD, director of the Division of Epidemiology and Clinical Application at the National Eye Institute (NEI), and lead author of the study report. “This 10-year data confirms that not only is the new formula safer, it’s actually better at slowing AMD progression.”
 
The original AREDS study, launched in 1996, investigated a daily dietary supplement formulation comprising 500 mg vitamin C, 400 IU vitamin E, 2 mg copper, 80 mg zinc, and 15 mg beta-carotene. It was found that this supplement formulation could significantly slow the progression of AMD from moderate to late disease, however, two concurrent studies on this population concluded that those who smoked and took beta-carotene had a substantial increase in lung cancer risk.
 
In 2006, AREDS2 began, in which the formulation swapped out the beta-carotene for 10mg of lutein and 2 mg of zeaxanthin instead – like beta-carotene, these two antioxidants are active in the retina. An AREDS study was given but only to participants who never smoked or had quit smoking, in order to compare the significance of each formulation.
 
At the end of the AREDS2 study period, which lasted five years, the researchers found that the lutein and zeaxanthin formulation didn’t increase lung cancer risk and reduced AMD progression risk by about 26%. After the completion of the five-year study period, the participants were all offered the final AREDS2 formulation that included lutein and zeaxanthin instead of beta-carotene.
 
The new report included a follow-up with 2,882 of the original 4,203 AREDS2 participants for an additional five years from the end of AREDS2 in 2011, collecting further information on AMD progression and lung cancer incidence. Even though all the participants had switched to the formula containing lutein and zeaxanthin after the end of the study period, the follow up study continued to show that beta-carotene increased risk of lung cancer for people who had ever smoked by nearly double. There was no increased risk for lung cancer in those receiving lutein/zeaxanthin. In addition, after 10 years, the group originally assigned to receive lutein/zeaxanthin had an additional 20% reduced risk of progression to late AMD compared to those originally assigned to receive beta-carotene.
 
“These results confirmed that switching our formula from beta-carotene to lutein and zeaxanthin was the right choice,” Chew said.