New research breakthrough published on June 30 offers prospect of further improved vision among those with healthy eyesight
European Research Council-funded Waterford research breakthrough offers prospect of further improved vision among those with healthy eyesight; Major potential implications for motorists, train drivers, pilots and sportspeople
Irish-based research published Thurs, June 30 in the international journal, Investigative Ophthalmology & Visual Science(IOVS), holds out the prospect of even sharper vision for those who already have good eyesight. Whereas most research in this area has focussed on corrective action for those who’ve already suffered vision loss as a result of eye disease, this new study concentrated on those with strong and healthy eyesight, and yet found marked improvements in vision among those who received specific dietary supplements over a year.
The results of this study have important implications for those who rely on their vision for professional reasons, such as high-performance sportspeople (most obviously golfers, hurlers, cricketers, tennis and baseball players), motorists, train drivers, pilots, police and military marksmen and those involved in quality control; the study – entitled CREST (Central Retinal Enrichment Supplementation Trials) – was conducted by the Macular Pigment Research Group at Nutrition Research Centre Ireland (NRCI). NRCI is based at Carriganore House in Waterford, and is part of the School of Health Sciences at Waterford Institute of Technology.
This study, the first rigidly-designed study of its kind, was funded by the European Research Council and involved 105 volunteers undergoing complex test of vision over a 12-month period. Of the one hundred and five subjects, 53 received daily supplements while 52 received a placebo (the control group). The outcome unequivocally demonstrates that those receiving macular carotenoids – lutein, zeaxanthin and meso-zeaxanthin – enjoyed meaningful benefits to their visual function. The improvement recorded was primarily in people’s contrast sensitivity – how much contrast a person needs to see a target (i.e. how faint an object can you see).
Prof John Nolan, Principal Investigator for the CREST study and founder of the Nutrition Research Centre Ireland, said: “All of us involved in this research are tremendously excited about the outcome – not only from a scientific perspective but also because of the significant benefits it will have for a wide range of people. Many people may already consider themselves to have ‘good’ eyesight, but now we know that many of these would benefit from appropriate supplementation.
“To take the example of drivers on our busy roads, improvements in contrast sensitivity, such as we have seen in our study population, would allow for earlier and more accurate detection of moving and non-moving objects in our field of view, and will therefore improve driving safety.
“Sportspeople – especially those in fast ballgames – also stand to benefit greatly, and we were delighted to have Noel Connors, the Waterford senior hurler and All-Star undergo testing at our vision research centre.”
Prof Stephen Beatty added that there are also significant quality of life implications emanating from the research findings – “There has been an understandable focus in research to date on aiding those with failing eyesight as a result of disease. What this latest work demonstrates is that people who are free of eye disease (especially if they are lacking the nutrient in the eye) will experience improved vision as a result of appropriate supplementation.
“Clearly this will enhance one’s quality of life in everyday activities, such as enjoying a pleasant view, but these improvements in contrast sensitivity will also make it easier to read printed text, thereby easing eye strain and fatigue in the workplace and at home. In short, these findings have important implications for those seeking maximum visual performance, whether for work or leisure.”
The publication was prepared by the Waterford-based research team of Prof Nolan; Prof Beatty; Rebecca Power; Jessica Dennison; Jim Stack; David Kelly; Rachel Moran; Kwadwo O Akuffo and Laura Corcoran and were joined by Prof Jim Stringham from the Nutritional Neuroscience Laboratory, Dept of Physiology & Pharmacology, University of Georgia, U.S.A.
Red Pepper Sauce:
Chop 1 red bell pepper- medium sized dice
Peel 1 small red beet, chop small dice
Water to cover the pepper and beets
1 Bay leaf
Place all ingredients in a small pot cover with water and bring to a boil then simmer until the vegetables are soft. (About 15-20 minutes)Then remove bay leaf and puree with a hand stick blender or a blender. If it is too thick thin it out with a little water to get a nice sauce texture, add a tablespoon of olive oil for richness and shine. (optional)
Set aside in a warm place.
Rainbow Swiss Chard:
Trim the bottoms of the chard, chop 1 clove of garlic, place in a medium sized sauté pan- cover with water, bring to a boil and simmer gently (7-8 minutes)
Strain set aside in a warm place on the stove. ( Drizzle a little olive oil on the leaves- optional)
Season both sides of the fish with S&P or your favorite dry spice blend
In a large sauté pan heat the pan on medium high heat, add the olive oil to cover the bottom of the pan then add your Tilapia filets.
Make sure pan is hot before adding filets so the Tilapia does not stick.
Cook a couple of minutes on each side until nice and golden brown. Remove from pan and drain on a paper towel.
TO PLATE THE DISH
Place the steamed rainbow swiss chard and garlic in the center of your plate. Add the Tilapia filets in a cross pattern on top of the swiss chard. Spoon the red pepper sauce around the plate. Garnish with Italian Parsley and Enjoy!
This is an excellent dish. It’s healthy, quick and packed with lutein and zeaxanthin! Lutein and zeaxanthin are 2 of 3 essential carotenoids proven to enrich macular pigment, enhance vision, and help preserve vision.
To learn about the verification of the third essential carotenoid meso-zeaxanthin found in fish check out the following scientific article!
· with Fresh Corn Polenta, Warm Kale Salad, & Berry Sauce ·
3/4 cup quality corn meal
1 ear corn
1 bay leaf
1/4 red bell pepper
1/4 orange bell pepper
1 clove garlic
2 links hot sausage
2 cups baby kale
2 tablespoon blackberry jam
1 tablespoon dried cherries
2 tablespoon balsamic vinegar
2 tablespoon good red wine
S&P to taste
Simmer Hot Sausage for 10 minutes in a pot covered with water. Drain and place cooked sausage in the cooler. When cool remove casings, and slice sausage on the bias ¾” set aside.
Remove corn from the cob set aside. Add corn cob to small pot with bay leaf, cover with 5 cups cold water bring to boil and simmer 15 minutes, strain and reserve corn broth and bay leaf. Rinse baby kale and dry on a paper towel. (cooking tip – ALWAYS WASH YOUR VEGETABLES).
Prepare berry sauce: cover dried cherries with red wine and balsamic vinegar set aside 20 minutes to soften the cherries. Add blackberry jam to a bowl with balsamic vinegar, soaked cherries and wine, whisk well, little bit of crack pepper- set aside.
Bring corn broth to a boil with the bay leaf slowly add cornmeal with the corn kernels, and constantly stir with a whisk, cook over medium heat for 10 minutes, if polenta gets to thick add water as you are cooking to adjust the texture, season S&P to taste. Turn off the heat cover with lid to keep warm- set aside.
In a non-stick pan put pan on medium heat, add the olive oil and begin browning the sausage and julienne sliced peppers, with crushed garlic. Keep warm once sausage is caramelized on very low heat- can cover as well.
In a small sauté pan add tablespoon of olive oil, add the kale, S&P to taste and quickly sauté on high heat for 15-20 seconds just to wilt.
TO PLATE THE DISH
Spoon in corn polenta on a plate, add the sausage and peppers with roasted garlic. Place warm kale on plate and spoon over berry sauce with cherries. Serve immediately. Garnish with basil or your favorite herb. Enjoy!
This is the perfect dish for spring. The warm soft polenta is comfort food and rich in lutein. The spicy sausage contains paprika which has ocular health benefits. The julienne red and orange peppers are an excellent source of zeaxanthin. Warm kale salad is an excellent source of lutein. To summarize the corn, peppers, kale, blackberry jam, and dried cherries are all essential ingredients packed with anti-oxidants to enrich your macular pigment, enhance your vision, and help preserve your vision.
This is a fun easy recipe and so delicious! The corn broth will give greater flavor to the polenta, the balance of balsamic vinegar and blackberry jam with cherries helps cut the richness of the spicy sausage. Make it for both yourself and friends and family!
Don’t forget…To maintain good Ocular Health always eat your Fruits and Veggies!
The idea that a select few dietary nutrients could serve functions as varied as normal brain development, eye protection, skin protection, cardiovascular health, reaction time improvement, cognitive function enhancement, and age-related disease prevention at first seems preposterous. Indeed, any reasonable person approached with such a claim should be highly skeptical, and ask for the evidence. In the following [article], I will provide the evidence for lutein (L), zeaxanthin (Z), and mesozeaxanthin (MZ) as the nutrients described above, and characterize how they play a role in normal development, enhanced function, and health across the lifespan.
Lutein and Zeaxanthin are naturally-occurring carotenoid pigments found primarily in leafy-green vegetables, such as spinach and kale (Sommerburg et al. 1998). They are not synthesized by the body, and so must be obtained from dietary sources, or supplements. Those who have diets rich in leafy greens, or supplement with sufficient L and Z, tend to have higher blood and tissue concentrations of these carotenoids (Ciulla et al. 2001; Bone et al. 2003). Although somewhat rare, trace amounts of MZ are present in the diet in various parts of the world – it is found in 21 species of fish, shrimp and sea turtles, as well as eggs (due to supplementation of chicken feed) in California and Mexico (Maoka et al. 1986; Nolan et al. 2013). Importantly, MZ has been shown to be converted from L in the retina; it is found in high densities in the very center of the retina, where it affords protection and performance to the vulnerable neural tissue there. In terms of dietary response, the body appears to recognize MZ, as it has been shown to be readily deposited in the retina when taken in supplement form (Bone et al. 2007; Loughman et al. 2012). L, Z, and MZ serve very important functions in the body. Firstly, they are extremely potent antioxidants. L, Z, and MZ’s antioxidant capability enables them to protect bodily tissues against damaging free-radical oxygen (Krinsky et al. 2003). This is an extremely important function, because if free-radical reactions continue unabated they can lead ultimately to DNA damage, which manifests as tissue degeneration or cancer. We often fail to appreciate the high-energy, somewhat violent nature of the chemistry of our body; for this reason the body builds a defense against oxidation in key areas, such as the retina and brain, where it is most needed. With regard to L, Z, and MZ, this preferential placement in vulnerable tissues starts very early.
The Macular Carotenoids in the Womb / Infancy / Childhood
Until fairly recently, the role of L, Z, and MZ in health was thought to be limited to helping protect against the development of age-related macular degeneration (AMD; e.g. Seddon et al. 1994). Over the last 6-7 years, however, solid evidence from prenatal and neonatal research indicates an important role for these carotenoids in the very beginning of life. For example, it has been shown that L and Z play a major role in the early development of neural tissue in utero: At about 6 weeks of gestation (before the retina starts to develop), L and Z are transferred via the umbilical cord (Rubin et al. 2012) from the mother to the fetus, and start to accumulate in an ocular reservoir called the vitreous humor. At 20 weeks gestation, as the retina begins to be “built,” L and Z are diverted from the vitreous humor into the now-forming retinal tissue, where they serve as antioxidants during the volatile, extremely high metabolic environment of neurogenesis (Panova et al. 2007). Because oxygen is one of the major building blocks of neural tissue, the potential for free-radical oxidative stress and damage is high; based on the conspicuous timing of passage from the vitreous humor to the retina, coupled with the antioxidant capability of L and Z, it is not unreasonable to suggest that they play a crucial, early role in the development of neural tissues. L in particular is also found in high concentrations in the infant brain (Vishwanathan et al. 2011). This is true of no other carotenoid. The development of the brain occurs so rapidly and with such metabolic intensity that it makes sense the body would put L (a potent antioxidant) in an area of such high oxidative stress. Additionally, because much neurodevelopment in the brain and retina occurs after birth, L no doubt maintains this role well into childhood. In fact, an argument could be made that children, despite their relatively small stature, actually need as much or more daily L (and also Z and MZ) as adults. This is for two reasons: 1) Children are still developing, and are thus using more oxygen to build tissues. More oxygen leads to increased potential for oxidative stress, and L, Z, and MZ can help to reduce it. 2) Tissue stores of L, Z, and MZ (such as the retina, brain, and adipose tissue) are relatively empty. By ensuring that a meaningful amount of these carotenoids is included in a child’s diet, accumulation in these critical areas of the body is promoted. This would ultimately lead to enhanced protection into adulthood and beyond.
Lutein, Zeaxanthin, and Mesozeaxanthin in Adulthood / Old Age
In adults, L, Z, and MZ in the retina (where they are collectively referred to as the “macular carotenoids”) have been shown to be positively associated with a number of important functions related to both health and performance. There are several visual performance advantages, including increasing visual processing speed (Hammond & Wooten, 2005), and many parameters of visual performance in bright light environments. On average, subjects with higher concentrations of the macular carotenoids are able to maintain visibility of a flickering light at higher frequencies than those with lower retinal lutein (who see the light as a stable, solid disc of light). In other words, those subjects with higher concentrations of L, Z, and MZ in their retinas have faster visual systems; this manifests as faster reaction time performance. High macular carotenoid concentration has also been shown to substantially improve visual performance in bright light environments (i.e. glare). These effects include reduced visual discomfort in bright light (Stringham et al. 2003; 2004; 2011), increased ability to see through glare (Stringham and Hammond, 2007; 2008), and decreased photostress recovery time (recovering a visual target after exposure to an extremely bright light; Stringham and Hammond, 2007; 2008; Stringham et al. 2011). More recently, the macular carotenoids have been shown to be associated with better cognitive function in people over 50 – subjects with higher macular carotenoid concentrations (which have been shown to be correlated to brain levels of L and Z – Vishwanathan et al. 2013) perform better on cognitive tasks related long-term memory and decision-making (Feeney et al. 2013). Additionally, in a recent study of deceased centenarians (those who had lived to over 100 years of age), Johnson et al. (2013) found that brain concentrations of L were significantly higher than any other carotenoid, especially in areas that serve cognitive function, such as the frontal and temporal lobes. This suggests not only that L appears to be very important to brain function well into old age, but also (based on the areas into which it is deposited) that L is important in preserving high-level cognitive function. L also appears to play a protective role in cardiovascular health, in that it inhibits vascular cell adhesion molecules from accumulating atherosclerotic plaques (Kailora et al. 2006). Over time, this function leads to a greatly reduced risk for developing atherosclerosis, and cardiovascular disease. Interestingly, L and Z (by virtue of their deposition throughout the layers of the skin) also appear to provide protection from UVB-induced erythema (i.e. sunburn; Heinrich et al. 2003). Moreover, L and Z were shown to help manage and limit damage already caused by UVB light. Perhaps the most exciting new research direction for L, Z, and MZ involves their potential role in preventing the onset, or slowing the progression, of cognitive decline. As noted above, in several studies, people over 50 years of age performed significantly better on cognitive tasks as a function of their macular carotenoid concentration. This idea was recently investigated by Nolan et al. (2014) in a study of early-stage Alzheimer’s disease patients versus normal, age-matched controls. The Alzheimer’s patients were shown to have significantly lower macular carotenoid concentrations than the control subjects. This finding suggests that, as in AMD, perhaps the macular carotenoids are preventing cumulative damage over the lifespan that can, if left unchecked, produce neural damage that ultimately lead to cognitive impairment. In a follow-up study (Nolan et al. 2015), Alzheimer’s disease patients were found to respond positively in the retina to macular carotenoid supplementation, which suggests that the body maintains the ability to absorb and use these carotenoids in neural tissue, and that they may offer some potential benefit in increased concentrations. Lastly, as noted earlier, there is a well-established relationship between high concentrations of macular carotenoids and a reduced risk for developing AMD, the leading cause of blindness in people over 60 in the United States (National Eye Institute). Importantly, there is evidence that even after the onset of AMD symptoms (e.g. mild distortions of central vision), macular carotenoid supplementation can slow down, or even perhaps stop the progression of the disease (Richer et al. 2004). It appears therefore that the macular carotenoids have not only long-term protective effects on tissues, but also can have acute beneficial effects as well.
In summary, L, Z, and MZ appear to provide meaningful, significant benefits across the lifespan. The more we learn about these carotenoids, the more it becomes apparent that they are crucial to normal development, health, and performance. From their involvement very early in protecting developing neural tissues, to reducing cumulative damage that results in age-related disease, it is clear that L, Z, and MZ are meant to play a significant role in human development, performance, and aging. Although L, Z, and MZ are not considered essential nutrients (i.e., vitamins), based on the available scientific evidence, they may certainly be considered essential for optimal health and performance. Lastly, given our ever-increasing lifespan, any factor that can plausibly extend to us a benefit that can ensure more healthful years of life is always welcome. L, Z, and MZ appear to be such factors.
About the author: James Stringham, Ph.D.
Dr. Stringham earned his doctoral degree in experimental psychology from the University of New Hampshire in 2003. During postdoctoral appointments at the Schepens Eye Research Institute at Harvard Medical School and the Medical College of Georgia, he conducted research on ocular lutein, age‐related macular degeneration, the effects of intense light on visual performance, and plasticity of the visual system. Dr. Stringham then took a position as a visiting assistant professor at the University of Georgia, where he continued and extended a research program involving lutein and many facets of visual performance. In 2007, he became a senior vision scientist in the Air Force Research Laboratory (AFRL), where he was involved in extensive testing of the effects of lutein and zeaxanthin on human visual performance. Currently he is a research scientist at the University of Georgia, where his research includes studying the effects of lutein, zeaxanthin, and mesozeaxanthin on a variety of human physiological, health, and performance parameters.
Bone RA, Landrum JT, Guerra LH, Ruiz CA. Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans. J Nutr. 2003. 133(4):992-8.
Ciulla, T. A., Curran-Celantano, J., Cooper, D. A., Hammond, B. R., Jr., Danis, R. P., Pratt, L. M., Riccardi, K. A., & Filloon, T. G. (2001). Macular pigment optical density in a midwestern sample. Ophthalmology, 108(4), 730-737.
Feeney J, Finucane C, Savva GM, Cronin H, Beatty S, Nolan JM, Kenny RA. (2013). Low macular pigment optical density is associated with lower cognitive performance in a large, population-based sample of older adults. Neurobiol Aging. 34(11):2449-56.
Seddon, J. M., Ajani, U. A., Sperduto, R. D., Hiller, R., Blair, N., Burton, T. C., Farber, M. D., Gragoudas, E. S., Haller, J., Miller, D. T., & et al. (1994). Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA : the journal of the American Medical Association, 272, 1413-1420.
Rubin LP, Chan GM, Barrett-Reis BM, Fulton AB, Hansen RM, Ashmeade TL, Oliver JS, Mackey AD, Dimmit RA, Hartmann EE, Adamkin DH. (2012). Effect of carotenoid supplementation on plasma carotenoids, inflammation and visual development in preterm infants. J Perinatol. 32(6):418-24.
Krinsky NI, Landrum JT, Bone RA. (2003). Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Ann Rev Nutr. 23:171–201.
Nolan JM, Loskutova E, Howard AN, Moran R, Mulcahy R, Stack J, Bolger M, Dennison J, Akuffo KO, Owens N, Thurnham DI, Beatty S (2014). Macular pigment, visual function, and macular disease among subjects with Alzheimer’s disease: an exploratory study. J Alzheimers Dis. 42(4):1191-202.
Nolan JM, Loskutova E, Howard A, Mulcahy R, Moran R, Stack J, Bolger M, Coen RF, Dennison J, Akuffo KO, Owens N, Power R, Thurnham D, Beatty S (2015). The impact of supplemental macular carotenoids in Alzheimer’s disease: a randomized clinical trial. J Alzheimers Dis. 44(4):1157-69.
Panova I, Iakovleva MA, Fel’dman TB, Zak PP, Tatikolov AS, Sukhikh GT, Ostrovskiĭ MA. (2007). Detection of carotenoids in the vitreous body of the human eye during prenatal development. Bull Exper Biol Med. 144(5):681-683.
Vishwanathan R, Neuringer M, Schalch W, and Johnson E (2011). Lutein (L) and zeaxanthin (Z) levels in retina are related to levels in the brain. FASEB meeting abstract supplement 344.1; April, 2011.
Hammond, B. R., Jr., & Wooten, B. R. (2005). CFF thresholds: relation to macular pigment optical density. Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians, 25, 315-319.
National Eye Institute: Fact sheet, leading causes of blindness in the U.S. Webpage: http://www.nei.nih.gov/health/fact_sheet.asp
Gonzalez, S., Astner S., et al. (2003). “Dietary lutein/zeaxanthin decreases ultraviolet B-induced light epidermal hyperproliferation and acute inflammation in hairless mice.” J Invest Dermatol 121: 399-405.
Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, Pei K, Tsipursky M, Nyland J. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry. 2004. 75(4): 216-30.
Heinrich U, Gärtner C, Wiebusch M, Eichler O, Sies H, Tronnier H, Stahl W. Supplementation with beta-carotene or a similar amount of mixed carotenoids protects humans from UV-induced erythema. J Nutr. 2003. 133(1):98-101.
Kaliora AC, Dedoussis GV, Schmidt H. (2006). Dietary antioxidants in preventing atherogenesis. Atherosclerosis. 187(1):1-17.
Vishwanathan R, Iannaccone A, Scott TM, Kritchevsky SB, Jennings BJ, Carboni G, Forma G, Satterfield S, Harris T, Johnson KC, Schalch W, Renzi LM, Rosano C, Johnson EJ (2014). Macular pigment optical density is related to cognitive function in older people. Age Ageing 43, 271-275.
Sommerburg O, Keunen JE, Bird AC, van Kuijk FJ (1998). Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes. Br J Ophthalmol 82(8):907-910. (NHANES 2003-2004).
Stringham JM, Fuld K, Wenzel AJ. Action spectrum for photophobia. J Opt Soc Am A Opt Image Sci Vis. 2003;20(10): 1852-1858.
Stringham JM, Fuld K, Wenzel AJ. Spatial properties of photophobia. Invest Ophthalmol Vis Sci. 2004;45:3838-3848.
Stringham JM, Hammond BR, Jr. The glare hypothesis of macular pigment function. Optom Vis Sci. 2007;84(9):859-64.
Stringham JM, Hammond BR. (2008). Macular pigment and visual performance under glare conditions. Optom Vis Sci. 85(2):82-8.
Stringham JM, Garcia PV, Smith PA, McLin LN, Foutch BK. Macular Pigment and Visual Performance in Glare: Benefits for Photostress Recovery, Disability Glare, and Visual Discomfort. Invest Ophthalmol Vis Sci. 2011; 52:7406–7415.
Lutein and the two zeaxanthin isomers, RR-zeaxanthin (3R,3’R-zeaxanthin) and meso-zeaxanthin (3R,3’S-RS-zeaxanthin) are the only three carotenoids found in the eye, specifically in the macula of the retina (Bone et al. 1997). RR-zeaxanthin and meso-zeaxanthin are both considered zeaxanthin; they differ only in the spatial orientation of the hydroxyl group on the C3’ chiral position (Nolan et al. 2013 – see Figure 1). They are obtained via the diet, and concentrated in the central retina (termed the macula – the region of the retina responsible for highest visual performance). The location of their respective areas of deposition is highly specific: lutein is the dominant carotenoid in the peripheral macula, RR-zeaxanthin in the mid-peripheral macula and meso-zeaxanthin at the center of the macula (Bone et al. 1997).
Each of these carotenoids plays an important role in protecting the retina and enhancing visual performance (Bone et al. 2003; Thurnham & Howard, 2013; Stringham et al. 2011). The characterization and functions of lutein and RR-zeaxanthin are well known, and the science behind these two xanthophylls has grown at a steady rate. Meso-zeaxanthin has historically been incorrectly coupled with RR-zeaxanthin as an impurity or its isomer, and the measurement of meso-zeaxanthin in serum and foods had largely been ignored until awareness of its specific role in the eye emerged. One of the primary functions of the macular carotenoids is quenching potentially damaging free radical oxygen species (ROS). Each of the macular carotenoids is a potent antioxidant with specific targets. Meso-zeaxanthin is the most potent of the three, followed by RR-zeaxanthin, which is twice as potent as lutein in quenching reactive oxygen species (Bhosale & Bernstein, 2005). The protective role of lutein is more pronounced within the cellular membrane. Meso-zeaxanthin is located at the very center of the macula, the focal point of visual function. Its central location and stronger antioxidant potential make Meso-zeaxanthin critical in protecting the tissue at most risk – the center of the fovea has the highest packing density of photoreceptors, and maintains the highest metabolic rate, and light exposure – and therefore is under nearly constant assault (see Table 1 for specific locations of deposition for the three macular carotenoids). It is quite advantageous, therefore, that the tissue at most risk is protected by the strongest antioxidant of the three. meso-zeaxanthin also provides the best protection for the lipid membrane (Landrum et al. 1999; Subczynski et al. 2010). In terms of overall retinal protection, a mixture of the three macular carotenoids at a ratio of 1:1:1 has been shown to quench singlet oxygen more effectively than any of the three individually (Li et al. 2010). Meso-zeaxanthin and RR-zeaxanthin are perpendicular to the cell membranes to better protect the lipid membrane from oxidation and absorb similar wavelengths of high energy light (Sujak et al. 1999). Lutein is both parallel and perpendicular to the cell membrane, and also oriented near the surface of the cell membrane; this makes it a better filter of blue light. Because lutein and the zeaxanthin isomers absorb different wavelengths of light, together, the three absorb a broader spectrum of high energy light, which offers greater protection of retinal tissue (see Figure 2 for a pictorial representation of this phenomenon). Structural differences, orientation to cell membranes, macular location and differing absorption spectra therefore help the three macular carotenoids work together to provide superior filtration of blue light as compared to each individually (Billsten et al. 2003; Li et al. 2010; Nolan et al. 2013).
In addition, the three macular carotenoids work together for optimal eye health and visual function. Each individually and in combination with each other has been shown to increase macular pigment optical density. But the typical central peak of macular pigment optical density, found in the very center of the fovea, can be realized in subjects with atypical macular pigment spatial profiles at baseline only when supplemented with all three macular carotenoids (Nolan et al. 2012). This suggests that a combination of all three macular carotenoids is required to produce what appears to be a normal density distribution within the retina, and hence most likely normal retinal health and function. In terms of visual performance, increased density of the macular carotenoids is associated with faster visual processing (Hammond and Wooten, 2005), significantly improved visual performance in glare (Stringham et al. 2007; 2008; 2011; 2013) and reduced visual discomfort in bright light (Stringham et al. 2003; 2004; 2011; 2013).
Meso-zeaxanthin is the most recently characterized of the three retinal carotenoids, and is often found in trace amounts within commercially available lutein and RR-zeaxanthin supplements (ranging from 0.02-0.07% if chiral analysis is performed [Nolan et al. 2013]). As such, whether as dietary intake or part of lutein and/or zeaxanthin isomer(s) supplementation, Meso-zeaxanthin has already been part of studies investigating the nutritional impact on visual performance and AMD risk reduction. There are over 70 lutein studies at doses of 6-40mg, over 10 RR-zeaxanthin studies at doses of 1-20mg and several meso-zeaxanthin studies at doses of 8-14.9mg. Science continues to develop around the role of meso-zeaxanthin in eye health, and it is already established as a critical macular carotenoid with a specific function in ocular health. Today the significance of meso-zeaxanthin in the retina is well-established (e.g., Thurnam et al. 2008). Meso-zeaxanthin has proven bioavailability in humans (Thurnham et al. 2008), and has also been shown to be present in human serum pre-supplementation. Additionally, supplementation of meso-zeaxanthin has resulted in both increased serum levels and macular pigment optical density (Connolly et al. 2010), which, given its exceptional antioxidant properties, bodes well for human health.
Due to meso-zeaxanthin’s relatively recent empirical characterization, there have been some concerns with regard to its safety. Studies of meso-zeaxanthin supplementation containing fairly high doses (e.g. Connolly et al. 2010), have produced no reports of adverse events. In addition, meso-zeaxanthin is considered safe for use in food and dietary supplements and it meets the regulatory criteria per an FDA-acknowledged GRAS notification (http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-foods-gen/documents/document/ucm275974.pdf). In addition, a supplement containing meso-zeaxanthin was proven to be unequivocally safe in a GLP toxicological study (Ravikrishnan et al. 2011). Meso-zeaxanthin is not only converted from lutein in the eye (Neuringer et al. 2004) but is also found in the diet. Trace amounts of meso-zeaxanthin are present in the diet in various parts of the world – it is found in 21 species of fish, shrimp and sea turtles, as well as eggs in California and Mexico (Maoka et al. 1986). Additionally, meso-zeaxanthin has been a component of a xanthophyll supplement added to chicken feed in Mexico over the last 10 – 15 years (Nolan et al. 2013). Because of the lack of awareness of meso-zeaxanthin and the previous difficulty in measuring this particular carotenoid, it had typically not been tested. It is possible therefore that its presence in the diet and serum has been potentially underreported and it is most likely available in more foods than we are aware of.
The eye contains three carotenoids – lutein and two zeaxanthin isomers (meso-zeaxanthin and RR-zeaxanthin) – each with a specific location and distinctive role in retinal protection and visual performance. In terms of supplementation, lutein was the first commercially available macular carotenoid. As the state of the science has progressed, the need for higher levels of RR-zeaxanthin was determined. It is now clear that meso-zeaxanthin plays a critical role alongside lutein and RR-zeaxanthin in eye health. Given the specialized locations and functions of each macular carotenoid, it is reasonable to suggest that that the best way to support eye health and visual performance is to consume all three macular carotenoids, via diet or supplementation.
Article by: James Stringham, Ph.D.
About the author: Dr. Stringham earned his doctoral degree in experimental psychology from the University of New Hampshire in 2003. During postdoctoral appointments at the Schepens Eye Research Institute at Harvard Medical School and the Medical College of Georgia, he conducted research on ocular lutein, age‐related macular degeneration, the effects of intense light on visual performance, and plasticity of the visual system. Dr. Stringham then took a position as a visiting assistant professor at the University of Georgia, where he continued and extended a research program involving lutein and many facets of visual performance. In 2007, he became a senior vision scientist in the Air Force Research Laboratory (AFRL), where he was involved in extensive testing of the effects of lutein and zeaxanthin on human visual performance. Currently he is a research scientist at the University of Georgia, where his research includes studying the effects of lutein, zeaxanthin, and mesozeaxanthin on a variety of human physiological, health, and performance parameters.
Bone RA, Landrum JT, Friedes LM, Gomez CM, Kilburn MD, Menendez E, Vidal I, Wang W. (1997). Distribution of lutein and zeaxanthin stereoisomers in the human retina Exp Eye Res. 64(2):211-8.
Bone RA, Landrum JT, Guerra LH, Ruiz CA. (2003). Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans. J Nutr. 133(4):992-8.
Thurnham DI, Howard AN. (2013). Studies on RS-zeaxanthin for potential toxicity and mutagenicity. Food Chem Toxicol. 59:455-63.
Bhosale P, Bernstein PS. (2005). Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. Biochim Biophys Acta. 1740(2):116-21.
Landrum JT, Bone RA, Moore LL, Gomez CM. (1999). Analysis of zeaxanthin distribution within individual human retinas. Methods Enzymol. 299:457-67.
Sujak A, Gabrielska J, Grudziński W, Borc R, Mazurek P, Gruszecki WI. (1999). Lutein and zeaxanthin as protectors of lipid membranes against oxidative damage: the structural aspects. Arch Biochem Biophys. 371(2):301-7.
Li B, Ahmed F, Bernstein PS. (2010). Studies on the singlet oxygen scavenging mechanism of human macular pigment. Arch Biochem Biophys. 504(1):56-60.
Subczynski WK, Wisniewska A, Widomska J. (2010). Location of macular xanthophylls in the most vulnerable regions of photoreceptor outer-segment membranes. Arch Biochem Biophys. 504(1):61-6.
Sujak A, Gabrielska J, Grudziński W, Borc R, Mazurek P, Gruszecki WI. (1999). Lutein and zeaxanthin as protectors of lipid membranes against oxidative damage: the structural aspects. Arch Biochem Biophys. 371(2):301-7.
Billsten HH, Bhosale P, Yemelyanov A, Bernstein PS, Polívka T. (2003). Photophysical properties of xanthophylls in carotenoproteins from human retinas. Photochem Photobiol. 78(2):138-45.
Nolan JM, Meagher K, Kashani S, Beatty S. (2013). What is RS-zeaxanthin, and where does it come from? Eye (Lond). 27(8):899-905.
Nolan JM, Akkali MC, Loughman J, Howard AN, Beatty S. (2012). Macular carotenoid supplementation in subjects with atypical spatial profiles of macular pigment. Exp Eye Res. 101:9-15.
Thurnham DI, Trémel A, Howard AN. (2008). A supplementation study in human subjects with a combination of RS-zeaxanthin, (3R,3’R)-zeaxanthin and (3R,3’R,6’R)-lutein. Br J Nutr. 100(6):1307-14. Connolly EE, Beatty S, Thurnham DI, Loughman J, Howard AN, Stack J, Nolan JM. (2010). Augmentation of macular pigment following supplementation with all three macular carotenoids: an exploratory study. Curr Eye Res. 35(4):335-51.
Ravikrishnan R, Rusia S, Ilamurugan G, Salunkhe U, Deshpande J, Shankaranarayanan J, Shankaranarayana ML, Soni MG. (2011). Safety assessment of lutein and zeaxanthin (Lutemax 2020): subchronic toxicity and mutagenicity studies. Food Chem Toxicol. 49(11):2841-8.
Johnson EJ. (2002). The role of carotenoids in human health. Nutr Clin Care. 2002 Mar-Apr;5(2):56-65.
Bone RA, Landrum JT, Cao Y, Howard AN, Alvarez-Calderon F. (2007). Macular pigment response to a supplement containing meso-zeaxanthin, lutein and zeaxanthin. Nutr Metab (Lond). 11;4:12.
Maoka T, Arai A, Shimizu M, Matsuno T. (1986). The first isolation of enantiomeric and meso-zeaxanthin in nature. Comp Biochem Physiol B. 83(1):121-4.
Stringham JS, Fuld K, Wenzel AJ. Spatial properties of photophobia. Invest Ophthalmol Vis Sci. 2004;45(10):3848–3858.
Stringham JM, Hammond BR Jr. The glare hypothesis of macular pigment function. Optom Vis Sci. 2007;84(9):859–864.
Hammond BR Jr, Wooten BR. CFF thresholds: relation to macular pigment optical density. Ophthalmic Physiol Opt. 2005;25(4):315–319.
Stringham JM, Hammond BR Jr. Macular pigment and visual performance under glare conditions. Optom Vis Sci. 2008;85(2):82–88.
Stringham JM, Fuld K, Wenzel AJ. Action spectrum for photophobia. J Opt Soc Am A. 2003;20(10):1852–1858.
Stringham JM, Garcia PV, Smith PA, McLin LM, Foutch, BK. Invest Ophthalmol Vis Sci. 2011;52:7406–7415.
Stringham JM, Snodderly DM (2013). Enhancing performance while avoiding damage: a contribution of macular pigment. Invest Ophthalmol Vis Sci. 54:6298–6306.
Dr. Michael Tolentino is an Orlando, Florida retina specialist and early inventor of anti-VEGF injectable medications. In the September 2015 Primary Eyecare Optometry News article, he reported that several patients with wet AMD in his practice given Macuhealth twice daily to delay or defer injections resulted in improved acuity and resolution of subretinal/intraretinal fluid on OCT. He stated in the article, “While the results are presented as a case series, the response of these patients was equivalent to the typical response obtained after a course of anti-VEGF injections. Furthermore, Macuhealth worked synergistically with injections in patients previously unresponsive to injections.” He further states in the article, “I speculate that the potent antioxidative properties of these three carotenoids diminished the stimulus for VEGF upregulation. This supplement shows promise as a method for diminishing initiation and frequency of injections in patients with exudative AMD.”
Disclosures: Dr. Tolentino has no financial involvement in MacuHealth, Dr. David Nelson is a consultant for MacuHealth and authored the article in PCON covering the Carotenoid Conference. Click here to read the full article.
Summer is coming to an end, but there’s still ample time left to do some barbequing! You already know that when it comes to eye health, proper nutrition is imperative. Maintaining a balanced diet and consuming sufficient carotenoids (namely lutein, zeaxanthin and meso-zeaxanthin) can help to ensure that eye sight stays sharp and can even aid in warding off age-related macular degeneration. Said carotenoids are found primarily in leafy green vegetables and certain seafood. So, without further adieu, let’s get down to the details of how to prepare this eye-friendly grill out winner!!
(Ingredients and measurements to the side in blue)
• Rinse and gently pat dry kale fronds, garlic scape and Orange pepper
• Shred Kale fronds roughly ( I like the stalk too)
• With a sharp knife finely dice garlic scape and orange pepper
• Heat 2 tbs of California olive oil in a sauté pan on med-low and toss in finely diced aromatics (garlic scape and orange pepper)
• Sauté for 3 or 4 minutes before adding roughly shredded kale
• Sauté for 5-7 more minutes adding a small splash of purified water if moisture is needed.
• Toss with 1 tsp of pink crystal sea salt and fresh cracked pepper to taste!
• Take one large 16-20oz raw wild salmon filet (with the skin still on!) and rub it with 2 tbs of California olive oil, 1 tsp of pink crystal sea salt and fresh cracked pepper to taste.
• Grab one of your delicious Meyer lemons and slice it thinly into rounds. Place rounds on top of salmon filet.
• Let the salmon marinate on a covered plate for 15 minutes
• During this time, prepare grill. Also begin preparing braised kale
• Slice the other two lemons into halves
• Once grill is ready (coals are mostly white, or if fancy gas grill is up to temp)…
• Place salmon directly on grill skin side down
• Place halved Meyer lemons face down on grill
• Cover for 8-10 minutes
…Once salmon is grilled to a perfect medium rare, remove from grill with a metal spatula (and an assistant). Serve along side of your perfectly braised kale and grilled Meyer lemons! Enjoy.
About the author: Kirsten Stone hails from Portland, Oregon and grew up growing her own food on a farm. She has a lasting passion for nutrition as well as personal and global eye health.
Lloyd Snider, O.D. shares lecture topics and key takeaways from the Macular Carotenoids Conference held in Cambridge, UK July 8th-10, 2015.
I’m just back and over my jet lag from the Macular Carotenoids Conference 2015, held at Downing College, University of Cambridge, UK. It was an amazing three-day event where the world’s best researchers gathered for a spirited discussion on macular carotenoids. There were 24 lectures, each followed by questions from the attendees. Additionally, there were thirty-four posters presented which also had question and answer sessions. Poster Abstracts and Speaker Abstracts were published in the European Journal of Ophthalmology Supplement. (You can find the abstracts, here.)
Some of the topics covered:
Modifying sweet corn to increase carotenoid content
Childhood vegetable intake predicting adult MPOD
Macular pigment and cognitive function
A case of spontaneous MacTel 2 macular hole closure with carotenoid supplementation
L, Z, and MZ content in eggs from supplemented chickens
The impact of carotenoids and B vitamin supplements in Alzheimer patients
Serum response in humans to MZ enriched chicken eggs
Macular carotenoids in pre-and post-natal development
Macular carotenoids in breast milk
Clinical experience with macular carotenoids replacing injections in exudative AMD
Structural and functional response in glaucoma to carotenoid supplementation
Oxidative stress, carotenoids and dementia
Macular carotenoids, psychological stress, and general health status in young adults
Some of the things I learned:
There are differing xanthophyll contents in regions of the elderly brain
Macular pigment is important in cognition
Drusen have a high concentration of zinc.
Avocado helps with lutein uptake
Ganglion cell loss in glaucoma causes glare and dark adaptation problems
Glaucoma patients have lower macular pigment
With foveal involvement, more damage means slower photo stress recovery
There is a possible link between glaucoma and cognitive decline
After the lectures, expert guides gave us an historical tour of Cambridge and many of its colleges. Sampling some of the many pub offerings was delightful. We also had a great banquet with best poster awards for PhD candidates, as well as surprise entertainment from an opera-singing chef and maitre’d. They had the entire group singing and dancing around the hall.
The lectures should be available in the near future on video. We will let you know as soon as they are ready. The next Macular Carotenoids Conference meeting in Cambridge is slated for 2018. I hope to see you there. It is truly a unique experience and a worthwhile, intriguing meeting. Please plan ahead!
‘Could your eye vitamins be making macular degeneration worse?’ The alarming (yet intriguing) notion was recently discussed by Canadian optometrist, Richard Maharaj via his blog, Eyes on Eyes. In the article, Dr. Maharaj reviews some of the recent findings surrounding the important role of genetics in prescribing nutritional eye supplements.
Maharaj refers to the recent scientific research of Dr. Carl Awh et al. which has shown that up to 65% of AMD patients using an AREDS formulation may be on the wrong path due to their individual genetics. Dr. Awh, a vitreoretinal surgeon and leading author/researcher on genetically guided therapy for AMD claims that a subgroup of patients might actually be increasing the progression of AMD by supplementing with an AREDS formula.
It is no secret that the latest AREDS formula has, in some respects, become a standard treatment for dry AMD in recent years – and millions of patients have been prescribed the lutein, zeaxanthin, C, E, zinc and copper formula since AREDS2 was published. However, over the last few years, Awh et al. have discovered that patients experience geno-type dependent responses to AREDS’ antioxidant combination. In particular, Awh found that certain patients had unfavorable reactions to either zinc, anti-oxidants (C, E), or a combination of the two.
Maharaj describes Awh’s findings as ‘compelling enough’ for him to mark a change in the direction of care he delivers. He also voices his concern regarding AREDS’ inclusion of zinc, since zinc has been found to exacerbate certain retinal conditions. Plus, the upper daily limit of zinc by nutrition standards is a meager 40 mg, yet the AREDS formula somehow recommends a whopping 80 mg, causing Dr. Maharaj to further ponder the notion of blanketing all patients with the formula.
Though more research is necessary and some remain beholden to the AREDS formula, Dr. Maharaj notes that he is now, more so than ever, consciously considering the complexity of genetics when prescribing treatment for AMD. Indeed, the notion of personalized medicine is becoming more prominent — and an ‘AREDS for all’ approach is simply no longer appropriate.
If you’re interested in learning more about the role genetics may play in nutritional supplementation for eye disease, click here to view a presentation by Dr. Jerome Sherman on the subject.
A recent National Health and Nutrition Examination Survey has established a link between over consumption of calcium and a significantly increased risk of developing macular degeneration in the older population.
Researchers from the University of California evaluated 3,191 people aged 40 and over who participated in a national health survey. The group consisted of 248 people who were previously diagnosed with macular degeneration. Participants answered multiple questions regarding their use of dietary supplements and antacids, specifically. The survey also accounted for factors including age, sex, ethnicity, obesity smoking, alcohol consumption, cataract surgery, osteoporosis history, glaucoma and heart disease.
The results, published in the April 2015 issue of JAMA Ophthalmology, reported that individuals (aged 68 and older) supplementing with 800 mg of calcium per day were 85% more likely to be diagnosed with macular degeneration than those who do not supplement with calcium. The association between calcium supplementation and AMD was found to be more prominent in older individuals, likely due to the longer duration of calcium supplementation.
Indeed, some calcium is necessary for good health. However, studies like this one show that an over consumption of the mineral mixed with a lack of awareness may be serious concerns; especially considering that calcium supplementation is tremendously common among the older population, often due to concerns about osteoporosis and bone health. In fact, about 43% of the U.S. population (including approximately 70% of older women) say they take calcium supplements.
Researchers acknowledge the study’s limitations noting the possibility that some of the participant’s did not accurately report their use of calcium as well as the lack of research into the role that calcium from food and drink may play. Although the researchers have declined to make any new recommendations regarding calcium supplementation until further studies are conducted, individuals worried about developing AMD should continue to avoid smoking, wear protective eyewear when exposed to UV or blue light, eat a diet rich in leafy green vegetables and limit simple carbohydrates.
As usual, talk to your doctor before starting or discontinuing use of any supplement.