Lutein DRI: ‘A substantial undertaking but an opportunity for industry and the scientific community to work together’

DRIs exist for vitamins, minerals, essential fatty acids and essential amino acids.  Having a DRI would make lutein part of public nutrition policy, and could mean inclusion in large-scale publically-funded surveys such as the NHANES (National Health and Nutrition Examination Survey).

With the burden of age-related macular degeneration (AMD) falling on 25 to 30 million people worldwide, according to AMD Alliance International, there have been growing calls for a DRI for lutein.

The link between lutein and eye health was first reported in 1994 by Dr Johanna Seddon and her co-workers at Harvard University, who found a link between the intake of carotenoid-rich food, particularly dark green leafy vegetables like spinach, and a significant reduction in AMD (JAMA​, Vol. 272, pp. 1413-1420).

Research dollars have flowed into research (both public and private) exploring lutein and zeaxanthin for eye health, with many positive studies boosting the lutein/zeaxanthin market, worth approximately $145 million globally. In the US it is estimated to be between $90 and 100 million. 

“Although the science around lutein is substantial, additional research needs to be carried out on broader population groups to further support the DRI process,” ​explained Lynda Doyle, VP of Global Marketing, OmniActive Health Technologies. “This is an opportunity for industry and the scientific community to work together to evaluate the collection of data and build upon what has already been established.”​

A long and arduous process…​

Dietary Reference Intakes (DRIs) are a set of four nutrient reference values for healthy populations.  They include the Recommended Daily Allowance (RDA), Adequate Intake (AI), Estimated Average Requirement (EAR), and Tolerable Upper Intake Level (UL). 

“Each of these reference values distinguishes between gender and different life stages,” ​explained Dick Roberts, PhD, principal manager of scientific affairs & technical services for Kemin Human Nutrition and Health Division. “RDAs, AIs and ULs are dietary guidelines for individuals, whereas EARs provide guidelines for groups and populations. In addition, factors that might modify these guidelines, such as bioavailability of nutrients from different sources, nutrient-nutrient and nutrient-drug interactions, and intakes from food fortificants and supplements, are incorporated into the guidelines in much greater detail than previously.”​

OmniActive’s Doyle called the route for establishing DRIs for lutein as “a long and arduous process”, ​while Dr Roberts estimated the process could require more than five years to complete.

Duffy MacKay, ND, senior vice president, scientific and regulatory affairs for the Council for Responsible Nutrition (CRN), told us that a DRI for lutein would be difficult, and that CRN-International has been pushing the scientific community to think about DRIs for bioactives. “Without a new framework it’s going to be difficult,”​ said Dr MacKay. “If such a new framework got accepted then lutein would be one of the first to be considered.”​

For more information on CRN-I’s push for DRI’s for bioactives, please click HERE​.

Dr Roberts noted that Kemin has considered initiating the pursuit of at least an AI for lutein numerous time since launching FloraGLO Lutein in the mid-1990’s, but it has always difficult to justify such an effort since such an approval would apply to all suppliers of lutein, not just Kemin.  “Therefore, the return on investment has always been viewed as being low,”​ he said.

AREDS 2​

While any champagne to celebrate a DRI will have to be kept on ice, there were some celebrations last year when the much-anticipated results of the AREDS 2 study were published​. The data, published in the Journal of the American Medical Association​, indicated that adding lutein and zeaxanthin to the original AREDS supplement (vitamins C, E, beta-carotene and zinc) led to statistically significant reductions in the progression to advanced AMD. (The original AREDS study did not include lutein and zeaxanthin because these carotenoids were not commercially available when the protocol for that study was developed or even when the formulation used in the study was produced.)

The study also showed a 26% reduction in the risk of progression to advanced AMD for lutein and zeaxanthin beyond the effects of the AREDS supplement in persons with the lowest dietary intake of lutein and zeaxanthin, and an 18% reduction in the risk of progression to advanced AMD, particularly neovascular AMD, of lutein and zeaxanthin in head-to-head comparison with beta-carotene, said Dr Roberts.

AREDS2 also benefits for cataracts in the lutein and zeaxanthin supplementation group (JAMA Ophthalmol​, Vol. 132, pp. 142-149).

“AREDS1 and 2 were two landmark studies in the eye health category,”​ said OmniActive’s Doyle. “The findings of AREDS 2 further affirmed the safety and eye health benefits associated with lutein and zeaxanthin supplementation.  NIH's National Eye Institute made the recommendation to add lutein and zeaxanthin to the AREDS formulation and eliminate beta-carotene, which further speaks to the significance of the study results.”​

AREDS 3?​

Despite the AREDS findings, there is still a lot that is yet unknown about AMD, especially relative to the pathogenesis of AMD, said Kemin’s Dr Roberts.

With so many unanswered questions remaining unanswered will we get an AREDS3? CRN’s Dr MacKay said that any talk of another such study would depend on funding (AREDS 1 and 2 were funded by the National Eye Institute and by other components of the National Institutes of Health).

Dr MacKay said he thought we would see a study in the future along the lines of an AREDS3, while OmniActive’s Doyle said that there is still much science to evaluate, including the results of AREDS2. “As technology emerges and new trends are found in the world’s state of health, new goals will be determined,”​ she said. “A large-scale study such as AREDS3 could be a public initiative for the future, but this is yet to be seen.  However, this would be a nice-to-have, as we would now like to see additional research in different age groups and populations.”​

Kemin’s Dr Roberts was less convinced at the possibility of a third installment of the series. “Dr Emily Chew, the AREDS2 principal investigator at the National Eye Institute has publically indicated that no AREDS3 study is anticipated,” ​he said. “However, if research uncovers new insights that warrant a study following this hypothesis or even some other (yet to be determine) hypothesis, the decision on an AREDS3 study could change.  However, at the present time such a study seems unlikely. ​

“This is not to discount the possibility that other branches of the National Institutes of Health might take up the banner of lutein and zeaxanthin in human health, particularly in relation to the brain.  The relatively recent findings that lutein and zeaxanthin constitute 43% of all carotenoids in the brain and have effects upon cognition may provide an avenue for a clinical study evaluating the effects of these carotenoids upon cognitive health.  However, additional research, some of which is currently on-going, may provide the rationale for such a future study.”​

Doyle said that there remained a need for double blind placebo controlled studies in healthy populations of different gender and age groups, including functional and mechanism studies.  “It is becoming increasingly clear that the macular carotenoids show benefit for all age groups, from fetal development to the aging population and all in between,”​ she said.

Cost savings​

While DRIs for lutein may be still years away, the economic importance of the lutein and zeaxanthin dietary supplements was highlighted recently in an economic report commissioned by the CRN and performed by Frost & Sullivan. According to the report’s findings, lutein and zeaxanthin supplements for age-related eye diseases, including AMD and cataracts, could reduce the risk of these diseases by 23%, which would offer potential savings of $930 million, accounting for supplement costs and current supplement use (4%).

“Smart prevention is protecting your health and also protecting your wallet. Age-related eye disease poses risks that are debilitating and expensive, so supplementing with lutein and zeaxanthin can help reduce those risks,”​ said Dr MacKay.