|Photo courtesy: DSM|
A life without vision is, frankly, unimaginable. Scientists have repeatedly demonstrated the protective effects of carotenoids in individuals of all ages, from infants to seniors, but there continues to be a communication gap, as the concern remains strongest among the aging population, where it can be too late to take action.
More than 600 carotenoids are found in nature, but only a fraction play a known role in health and disease. Carotenoids are not made by the body and must be supplied from food or supplements. Their concentration in blood is associated with a variety of positive health outcomes, yet more than 95 out of 100 persons in the U.S. fall short on the carotenoid health index.
In researching nutraceuticals for better eye health, one class of compounds, the vitamin A-like carotenoids, stands out. And of these, two in particular—lutein and zeaxanthin—are proving to be highly impressive, on multiple levels and through different biochemical mechanisms, for their ability to protect eyesight.
Lutein and zeaxanthin are yellow-orange carotenoids, collectively called xanthophylls, which help filter blue light in targeted tissue. Lutein and zeaxanthin are present in the eyes, skin, blood, brain and other tissues. Their selective placement in ocular tissue (concentrated about 1,000-fold greater than in blood) form the macular pigment in the retina.
The macular pigment helps protect against the photo-oxidative effects of ultraviolet (UV) radiation and high-energy blue light. In the macula fovea—the area of focus in the back of the eyeball that is responsible for visual sharpness and acuity—the ratio of lutein to two isomers of zeaxanthin (RR-zeaxanthin and meso-zeaxanthin) is roughly 1:1:1, while lutein dominates the outer edges of the retina.
Increasing evidence suggests that lutein and zeaxanthin intake must be early and consistent to help maintain optimal eye health over a person’s lifetime. Although diets rich in fruits, vegetables and eggs increase tissue levels of lutein, zeaxanthin, lycopene and beta-carotene, it can be difficult to achieve ideal amounts through dietary sources alone.
Some xanthophylls are found naturally esterified with fatty acids. This form occurs, for example, mostly during fruit ripening. More commonly to the diet, the xanthophylls are in their free form, the form that most often occurs in green vegetables. Xanthophylls are de-esterified after absorption and transported (largely via HDL-cholesterol in the bloodstream). Esterification serves to protect the carotenoids, which are inherently unstable.
Fortunately, food technologists have devised ways to stabilize lutein and zeaxanthin and other reactive antioxidants. It is because of this that many functional foods and dietary supplements contain both esterified and free forms of lutein and zeaxanthin.
Lutein and zeaxanthin are the only carotenoids present in the retina and lens of the eye, where their proposed function is to protect against oxidative stress due to exposure to solar radiation. These xanthophylls have demonstrated the ability to block penetration of reactive oxygen into cell membranes and prevent oxidation of these highly susceptible areas. They both can neutralize most free-radical species and stimulate antioxidant enzymes.
Structurally, lutein and zeaxanthin are isomers that differ by the location of a single double bond. Zeaxanthin exists in three forms wherein 3R, 3’R-zeaxanthin and 3R, 3’S-zea-xanthin (mesozeaxanthin) are the predominant forms present in the macula of the retina.
Functionally, zeaxanthin has a stabilizing effect on cell membranes and appears to be more protective during prolonged sun exposure. Mesozeaxanthin is believed to have an even better antioxidant capacity than RR-zeaxanthin in preventing oxidation of membrane lipids. The multi-antioxidant combination of xanthophylls contributes to healthy vision and can provide broad-spectrum antioxidative protection for an aging population.
It should be stressed, however, that although these three xanthophylls found in the eye differ only slightly in their chemical structures, they are not redundant in regard to function. They appear to possess different photo-protective properties, thus packing a powerfully protective punch.
Clinical research has shown that, as dietary intake increases, absorption and deposition of lutein and zeaxanthin in the visual center increases, as well. Accordingly, some epidemiological studies have reported an inverse association between dietary intake, or serum and retinal levels of lutein and zeaxanthin, with the risk of developing ocular diseases, such as age-related macular degeneration (AMD) and cataracts.
Epidemiological data indicate that the average intake of lutein and zeaxanthin from dietary sources is in the range of only 1-2mg/day (approximately 0.01-0.03mg/kg body weight/day). In general, the ratio of lutein to zeaxanthin in natural dietary sources is approximately 5:1. Numerous studies have demonstrated that increased dietary intake of lutein and zeaxanthin is associated with increased macular pigment optical density (MPOD) in healthy adults. MPOD is the thickness or density of the protective layer of carotenoids in the macula.
In addition to significantly increasing MPOD, long-term supplementation with all three xanthophylls (10.6mg meso-zeaxanthin, 5.9mg lutein, 1.2mg zeaxanthin) has demonstrated improvements in eyesight, including visual performance and acuity; reduced glare sensitivity; enhanced contrast sensitivity; improved vision in dim light; and reduced chromatic blur.
During the landmark “Age-Related Eye Disease Study 2” (AREDS 2), when participants were ranked based on their dietary intakes of lutein and zeaxanthin, it was observed that supplementation with lutein and zeaxanthin appeared to have a significant effect with the lowest dietary intake levels. And, within that group, lutein and zeaxanthin were significantly associated with a 32% reduction in progression to cataract surgery.
A significant reduction in any cataract and/or severe cataracts was also observed with supplementation for those participants having low dietary intakes of lutein and zeaxanthin. The presence of lutein plus zeaxanthin resulted in an 18% reduction in the risk of progression to advanced age-related macular degeneration (AAMD) and a 22% reduction in the risk of progression to neovascular AMD.
In another study, 60 elderly veterans took 8mg zeaxanthin per day for 12 months. Results showed that the subjects experienced a greater recognition of detail, gained an improvement of 1.5 lines on the eye chart, experienced disappearance of blind spots and had an improved ability to drive at night, as related to better night vision.
In another, randomized, double-blind, placebo-controlled study of 120 Chinese drivers, supplementation with 20mg/day lutein for 12 months showed a trend towards an increase in spectacle-corrected visual acuity for the subjects. They also experienced significant increases in serum lutein, MPOD, contrast and glare sensitivity—especially in mesopic (poorly-illuminated) conditions and they also attained improved scores on driving subscale.
Carotenoids in Concert
Of the approximately 30 carotenoids identified in human serum (and breast milk), lycopene, beta-carotene and lutein are among the most abundant. Though not present in the eye, lycopene and beta-carotene also possess light-filtering and antioxidant characteristics. Recent research suggests further that these three dietary carotenoids together may play a crucial role in retinal development and function in infants, as well as in the body’s response to oxidative stress and inflammation.
In 2012, the team of L.P. Rubin, MD, et al, was the first to present results of a comprehensive, randomized, controlled trial designed to assess feasibility and potential benefits of supplementing preterm infant formulas with lutein, lycopene and beta-carotene. Specifically, this study demonstrated that lutein might improve neuroretinal health in preterm infants who were considered at risk for poor eye health. Included in the results was evidence that lutein-supplemented preterm infants had greater rod photoreceptor sensitivity, further suggesting a protective effect.
These new findings, in combination with some of the information already known about lutein and zeaxanthin’s roles in eye health, add to the theory that these xanthophylls help support eye health throughout the lifespan. And, in 2011, follow-up research by Eithne Connolly, MS.c., on lutein supplementation further supported previous research showing those carotenoids to be remarkably safe, even at very high doses. The results were presented with the AREDS2 at the Center for Food Safety and Applied Nutrition.
Xanthophylls are well-absorbed in the gastrointestinal tract, especially in conjunction with a lipid or a meal containing fats or oils. But, because of their unstable nature, they can greatly benefit from the assistance of delivery systems. Understanding this need, eye health ingredient suppliers continue to develop technologies which support a wide array of delivery platforms.
For manufacturers, it’s important to know that both free lutein and lutein esters are GRAS-affirmed. They also have been available in Europe, as well as the U.S., for many years. They typically are provided in powder form or in oleoresins or even microbeadlets. While able to stand up to temperatures typical to processing, carotenoid compounds are fat-soluble and so tend to be sensitive to light.
Microbeadlet encapsulation or molecular dispersion processes preserve the stability of highly labile carotenoids. The formats also allow carotenoids to be successfully incorporated into a variety of finished products. The technology has the added benefit of improving the bioavailability of poorly absorbed nutrients, such as lutein and zeaxanthin.
Through research and development, food technologists, with the assistance of innovative ingredient suppliers, have been able to stabilize lutein and zeaxanthin for the incorporation into functional foods. Their lipophilic (fat-loving) nature lends to their incorporation into foods containing fats which help stabilize and aid in absorption of these nutrients. Due to their continued efforts, food scientists have successfully incorporated lutein in to nutrition bars, powder drink mixes and candies.
New to the Eye
Astaxanthin is another natural carotenoid known for a wealth of health benefits. While its primary use in the U.S. market has been in cosmetics and cosmeceutical supplements, due to its strong ability to protect skin cells from the oxidative effects of UV light, it also has shown promise when it comes to providing the same benefits to the eyes.
A spate of recent scientific studies provide evidence suggesting that astaxanthin’s strong antioxidant protection can work in concert with other antioxidants, allowing it to be a valuable addition to eye health formulations. Possessing a molecular structure that allows it to insert itself across the cell membrane bi-layer, astaxanthin snags the reactive oxygen free radicals that damage cells.
Although it attained GRAS status in late 2010, astaxanthin’s use in foods and beverages has yet to take off, due to an overwhelming rush on supply. It is a key carotenoid to watch (see “Nutraceutical Health Benefits,” http://bit.ly/1aamoLR). However, recent technological developments have allowed for the availability of a nature-identical version of this carotenoid nutrient, increasing the availability and, it has been suggested, the antioxidant potency.
Additional emerging technologies are focused on improved microencapsulation techniques, mucoadhesive polymers and/or phospholipid suspensions. Microencapsulation functions by providing a biologically congruent outer layer, that, much like a beadlet, helps preserve the ingredient’s stability. It provides a protective barrier against heat, oxygen and light. In addition, it protects against enzyme activity, hormones or changes in pH, all of which can compromise the active components of an ingredient. Some microbeadlets have even been developed to specifically bind only to cell membranes in targeted tissue.
Mucoadhesive polymers are another emerging area of interest. Mucoadhesion allows either for two materials to be held together or for a synthetic or natural material to be held to biological tissue for an extended period of time. This property helps promote absorption. Mucoadhesive polymers have also helped suppliers navigate the difficulties of providing water- and fat-soluble nutrients to fluid environments wherein aqueous and lipid components co-exist—a perfect example of this being the eye.
These new delivery systems have been able to support targeted delivery, sustained release and safety of supplementation. They also have been shown to promote ease of transport through cell membranes, which may allow for increased bioavailability and efficiency of dosing.
Supplementing with products containing pure forms of lutein and zeaxanthin—such as lutein esters and free lutein, as well as lutein with enhanced levels of zeaxanthin isomers—and complementing formulations with these and other carotenoid compounds is a boon for processors targeting the concerns of an increasingly presbyopic population of aging Baby Boomers.
Incorporating these ingredients into functional foods, drinks and supplement products can be the best way to ensure that protective levels of these critical nutrients are achieved throughout the lifespan.