EYE CARE BILBERRY + LUTEIN RESEARCH
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Lutein belongs to the xanthophyll family of carotenoids , which are synthesized within dark green leafy plants, such as spinach and kale. The purified crystalline form of lutein has been generally recognized as being safe for supplementation into foods and beverages. It is one of the major constituents of macular pigment, a compound concentrated in the macula region of the retina that is responsible for fine feature vision.
It is a very well researched antioxidant, with the majority of scientific researches concluding how Lutein and Bilberry improves our eye health
- It helps to improve the Macular Pigment Optical Density and visual contrast
- As a strong antioxidant, it fights against oxidative stress in our eyes caused by blue light
Areas Of Scientific Research
LUTEIN - EYE
Lutein and zeaxanthin (L/Z)  are two fat-soluble antioxidants belonging to the class of carotenoids called xanthophylls. Along with their conversion isomer meso-zeaxanthin, they are the major constituents of macular pigment, a compound concentrated in the macula region of the retina that is responsible for fine-feature vision.
- In terms of tissue concentrations, the presence of lutein and zeaxanthin in the retina represent the highest seen among any other human tissue type
The macula lutea is located in the central and posterior portion of the retina and possesses the highest concentration of photoreceptors, which are responsible for central vision and high-resolution visual acuity. It is a circular area 5–6 mm in diameter that possesses a characteristic yellow pigment that is made up entirely of lutein and zeaxanthin
Age-related macular degeneration (AMD) is a degenerative process of the macula and is the principal cause of blindness among people aged 65 and older in Western countries. AMD can be classified into two categories: non-exudative (or dry) and exudative (or wet) AMD. The former is characterized by an accumulation of soft drusen caused by photo-oxidative damage and de-pigmentation of the retinal pigment epithelium. The latter is characterized by neovascularization of the macula, and accumulation of scar tissue.
- AMD is a multifactorial disease. Among the important risk factors for AMD are age, genetic susceptibility, sunlight exposure, cigarette smoking, and poor nutritional status.
L and Z are widely distributed in nature and are common in plants . Animals do not synthesize carotenoids. In primates, dietary L and its isomers are selectively concentrated in the visual system (eye and brain) over other carotenoids in the blood, comprising 80% to 90% of carotenoids in human eyes and the majority of carotenoids in the brain [4,5]. They are the exclusive carotenoids in the neural retina and lens .
- The context of food matters. For example, L and Z are more bioavailable in eggs than in spinach . Recent evidence suggests that this higher bioavailability may be the result of carotenoid presence within the lipid matrix of the egg and/or increased transfer to blood high-density lipoproteins (HDLs) [8,9,10,11]. In contrast to other carotenoids, at least half of these more polar carotenoids are carried on HDLs.
Only two carotenoids,  namely lutein and zeaxanthin are selectively accumulated in the human eye retina from blood plasma where more than twenty other carotenoids are available. The third carotenoid which is found in the human retina, meso-zeaxanthin is formed directly in the retina from lutein
Carotenoids have many biological effects and can function as antioxidants to protect eye tissues against free radicals . The only source of carotenoids for humans is food, and the carotenoid availability in plasma is critical in long term maintenance of adequate tissue levels.
- Lutein is present in many fruits and vegetables, whereas zeaxanthin is found only in a small number of fruits and vegetables, and in eggs. For example, in maize 85 mole% of the carotenoids are lutein and zeaxanthin. Interestingly, in most dark green vegetables, such as scallions, green lettuce, celery, spinach, and Brussels sprouts, only traces of zeaxanthin, the most prevalent macular pigment, were found. In our study, the highest amount of zeaxanthin was found in an orange pepper, which was not previously analyzed.
- The highest mole percentage of both lutein and zeaxanthin (89 mole%) was found in egg yolk. Since eggs have a high cholesterol content, restricted intake of eggs has been recommended for many years, since cholesterol is a risk factor for coronary artery disease. However, in recent years several studies were published showing that a higher intake of cholesterol through the addition of more eggs in the diet, results not only in an increase of serum cholesterol but also in an increase of HDL cholesterol. Since HDL cholesterol is protective against atherosclerosis, extra egg consumption may not change the risk index for ischaemic heart disease based on the cholesterol levels. The consumption of eggs could actually be beneficial in order to obtain a higher intake of lutein and zeaxanthin, and since it has no severe adverse effects on cardiac risk factors, the exclusion of eggs from the diet could be reconsidered.
- It was found that a diet rich in dark green leafy vegetables could decrease the risk of ARMD.
MACULAR PIGMENT OPTICAL DENSITY (MPOD)
L/Z (with the isomer mesozeaxanthin) accumulate in the retina of the eye and form the retinal macular pigment (MP) [14,15]. MP has several functions in improving visual performance and protecting against the damaging effects of light, and MP levels are used as a proxy for macular health—specifically to predict the likelihood of developing AMD.
Dietary supplementation with macular carotenoids for 6 to 24 months has been observed to increase MPOD in 36% (138) to 95% of subjects, with many studies suggesting estimates between these two extremes .
MP density levels appear to be a marker for L and Z status throughout the visual system . Better health of neurons in the eye and brain might speed transmission of visual impulses from the photoreceptors to the visual cortex in the brain and/or increase lateral neural connections on this path, improving the speed of resolving changes in visual stimuli [18,19,20,21].
Improved critical flicker-frequency thresholds, visual-motor reaction time, and visual processing speed have been observed in adults 18 to 32 years of age who received Z supplements, alone or with L and omega-3 fatty acids, for only four months . Increases in about 0.09 MPOD units through supplementation were estimated to significantly improve visual processing speed in these young, healthy adults. These findings, if replicated, suggest that high MP levels might improve vision function for people of all ages in tasks requiring quick responses, such as tasks in computer-related work.
- A group from the University of New Hampshire  examined the relationship between serum lutein, lutein intake and macular pigment density (MPD) in a group of 278 healthy volunteers . Their analysis revealed that both serum lutein and dietary lutein significantly correlate with MPD in a positive manner-the higher the level in serum or in the diet, the higher the MPD. These results are consistent with previous observational studies showing a protective effect of serum and dietary lutein against AMD [25,26].
- The Carotenoids in Age-Related Eye Disease Study , an ancillary study of the Women’s Health Initiative Study showed that women in the highest quintile category of diet or serum levels of lutein and zeaxanthin were 32% less likely to have nuclear cataracts as compared with those in the lowest quintile category . A cross-sectional study of 376 subjects found an inverse relationship between lens optical density (LOD) and MPOD, suggesting that lutein and zeaxanthin may retard aging of the lens .
Other studies also report  no significant change in MPOD at any eccentricity, at 3 or at 6 months, in subjects supplemented with a preparation that does not contain MZ or in subjects given placebo. In contrast, subjects supplemented with all three macular carotenoids exhibited a significant increase in MPOD at four of the five eccentricities tested, at 3 months and at 6 months.
AGE RELATED MACULAR DEGENERATION (AMD) & CATARACT
Epidemiological studies [31,32] have revealed that low macular pigment levels are associated with a higher risk of AMD. Several large observational studies demonstrated that high dietary intake and higher serum levels of L and Z are associated with a lower risk of AMD, especially late AMD.
- Randomized controlled clinical trials have revealed that supplementation of L and Z increases macular pigment density, improves visual function, and decreases the risk of progression of intermediate AMD to late AMD, especially neovascular AMD. Future studies may include additional assessments of the relationship between macular pigment and different genotypic and phenotypic forms of AMD, the optimum dosages of L, MZ, and Z, and the possible synergistic effects associated with supplementing with other nutrients. Current studies on preventive and therapeutic effects of L and Z on ROP, DR, and cataract have yielded varied results
In a group of age-matched AMD patients and controls , the average MPD was significantly lower in AMD patients compared to controls as long as the subjects were not consuming high dose lutein supplements. MPD, however, was significantly higher (in the normal range) in AMD patients consuming a lutein supplement (≥4 mg per day) relative to those not receiving the supplement. This study showed that lutein supplementation is associated with increased macular pigmentation and suggests that supplementation may contribute to maintaining eye health.
Visual function in patients with age-related cataracts who received the lutein supplements improved [34,35], suggesting that a higher intake of lutein, through lutein-rich fruit and vegetables or supplements, may have beneficial effects on the visual performance of people with age-related cataracts.
Dietary concentrations  between 6 and 20 mg per day of lutein have been associated with a reduced risk of ocular disorders such as cataracts and age-related macular degeneration [37,38]. The effects of lutein and other antioxidants in mitigating early-onset age-related ocular and neurological diseases have been well documented [39,40,41,42]. Macular pigments such as lutein have biochemical significance to ocular health by averting disease onset as well as sustaining visual functionality.
- It has been suggested that 6 mg of lutein per day , either through diet or using supplements is likely effective in reducing the risk of cataracts and AMD. Although the optimal dose for lutein supplementation has not been established yet, the most common dose in commercial products is 10 mg/day. Lutein is found in many natural products including broccoli, spinach, kale, corn, orange pepper, kiwi fruit, grapes, orange juice, zucchini, and squash. There is 44 mg of lutein per cup of cooked kale, 26 mg/cup of cooked spinach, and 3 mg/cup of broccoli.
Early functional abnormalities  of the central retina in the early AMD patients could be improved by lutein and zeaxanthin supplementation. These improvements may be potentially attributed to the elevations in MPOD.
Synergistic associations between diet, lifestyle and genes and risk of AMD have been shown, with unhealthy lifestyles associated with an increased AMD risk regardless of AMD risk genotype [45,46]. A number of dietary measures have been associated with slowing the progression of AMD. These include a diet rich in omega3 fatty acids , a diet with a lower dietary glycemic index [48,49] and intake of nutrients including vitamins C and E, betacarotene, zinc, selenium, B vitamins, folate and vitamin B12 and lutein and zeaxanthin [50,51,52,53].
- Furthermore, the study found a 32% risk reduction of neovascular AMD (RR 0.68; 95% CI 0.51, 0.92)  among those people who consumed the highest category of L/Z compared to those who consumed the lowest
ANTIOXIDANTS AGAINST BLUE LIGHT
L and Z, like all carotenoids, are potent antioxidants [55,56] and also reduce oxidative damage indirectly by light absorption (as described above). In the retinal pigment epithelium (RPE), lens, ciliary body, and iris, the presence of oxidized metabolites  suggests that L and Z protect against oxidative stress. Oxidative metabolism in the RPE is higher than anywhere else in the body; L and Z are two of many carotenoids contained in the RPE, and they are the predominant carotenoids in membranes .
Macular carotenoids are estimated to absorb 40% to 90% of incident blue light (depending on concentration); this absorption protects the retina from light-related damage  and reduces light scatter.
Only lutein and its coexistent isomer, zeaxanthin, are found in that portion of the eye where light is focused by the lens, namely, the macula lutea. Numerous studies  have shown that lutein and zeaxanthin may provide significant protection against the potential damage caused by light striking this portion of the retina. In the eye, lutein and zeaxanthin have been shown to filter high energy wavelengths of visible light and act as antioxidants to protect against the formation of reactive oxygen species and subsequent free radicals.
Bluelight absorption by macular xanthophylls is extremely important for young eyes, for which the lens transparency is almost 95% . During aging the lens gradually loses its transparency, become yellowish, and better filtrate UV and blue light. Thus, in older age, the blue light filtration performed by macular xanthophylls becomes relatively less important.
The accumulation of oxygen radicals and lipid peroxidation, resulting from increased retinal oxygen utilization, has been postulated as a mechanism for photoreceptor apoptosis . One of the major protective roles lutein has in the retina is to serve as an oxygen free radical scavenger during oxidative stress conditions. The ability of lutein to provide effective removal of free radicals, such as singlet oxygen particles, is primarily governed by the chemical structure of two hydroxyl groups acting as strong sinks for reactive oxygen species (Figure 2) [63,64,65]. Xanthophylls and carotenes are considered the most efficient singlet oxygen scavengers among the carotenoid families [66,67].
- Consistent with this , lutein has been demonstrated to have anti-inflammatory properties [69,70,71] and supplementation lowers circulating complement factor levels.
Light-induced retinal damage depends largely on the wavelength, exposure time, and intensity of light . F or instance, the blue light (440 nm) requires 100 times less intensity to cause damage than orange light (590 nm). The presence of carotenoids in the macula capable of absorbing light of the blue range wavelength would indicate that they serve a protective function. Specifically, lutein appears to play a specific role as a photoprotective agent, effectively screening out the damaging blue light from causing excessive damage on the photoreceptors.
- Combined with the fact that lutein and zeaxanthin are the only carotenoids found in the macula and comprise the macular pigment, this suggests that the observed protective effects of high fruit and vegetable intake may be due primarily to lutein and zeaxanthin intake.
Visual acuity reflects the ability to resolve objects that are in high contrast to their background, as measured by the ability to distinguish smaller and smaller letters at a given distance. Results of some but not all intervention studies [73,74,75,76,77,78,79,80] indicate improvements in visual acuity when L and/or Z are supplemented alone [81,82,83] or, more often, in conjunction with other antioxidants and/or omega-3 fatty acids [73,84,85,86,87,88].
- Three of seven randomized trials in >50 individuals with early or advanced AMD [89,90] or with diabetic retinopathy  indicate improvements in visual acuity.
- A recent meta-analysis of L and/or Z supplementation (six months to three years) in individuals with AMD indicates a significant protective effect  and a direct relationship between improvement in visual acuity and the change in MPOD level achieved.
In a study of middle-aged individuals, supplementation for six months with 20 mg L and/or Z resulted in significant improvement in visual acuity . This level (20 mg) is approximately five times the levels that are expected to be achieved if an individual follows dietary guidelines for fruit and vegetable intakes. Better L and Z status over a long period might also lead to better visual acuity in middle age and old age as a result of a lower risk for the common causes of visual impairment (see Lutein and Zeaxanthin Status in Relation to Disease section).
Regardless of whether MP improves the most common measure of acuity in indoor tests, it could help us see farther. It is estimated that a person with 1.0 density unit of MP can see 26% farther through the atmosphere than someone with little or no MP . This improvement in vision, which might have conferred an advantage for previous humans in hunting, gathering, and remaining safe from predators, would, in today's world, be of greatest benefit to people for whom long-range acuity is important, such as pilots and sailors.
Impairments in contrast sensitivity occur before visual acuity is affected by aging or disease. Contrast sensitivity is the ability to detect contrasts in levels of lightness or darkness of an object, or of colors, relative to the object's background. Detecting contrasts can be especially difficult in dim lighting, as occurs at dawn and twilight.
- An example would be the ability to distinguish the edges of stairs; in this case, better contrast sensitivity could reduce the likelihood of falls and improve confidence in walking down steps. Contrast sensitivity is well correlated with various aspects of visual ability, such as orientation and mobility, reading speed, and driving, and with the satisfaction of individuals with their visual function and how their visual ability affects their quality of life.
- Supplements containing L and Z at various amounts and taken for three months to three years have improved contrast sensitivity in most previous studies, including in young, healthy subjects, in people with early and/or advanced AMD, and in individuals with diabetes. Four of five randomized, placebo-controlled trials of solely L and/or Z isomers in >50 subjects observed improvements in spatial contrast sensitivity; results of one other trial did not. The long-term influences of L and Z status on contrast sensitivity in later life would include not only these short-term effects but also protection against age- and disease-related changes.
Macular Xanthophylls may not only act as a blue-light filter but also optimize visual performance. The layer of macular xanthophylls is believed to reduce chromatic aberrations, glare disability, and light scattering which enhance vision contrast.
Their unique presence in the centre of the macula implies an important role for L/Z in visual performance [ Antioxidant and blue light-filtering properties of L/Z for short wavelengths are hypothesised to protect the eye against AMD. The filtration of blue light reduces chromatic aberration which can enhance visual acuity and sensitivity.
- Results of this meta-analysis suggest that L/Z supplementation is associated with significant improvements in visual acuity and contrast sensitivity in a dose-response manner
In conclusion, the antioxidant, anti-inflammatory and blue light-absorptive properties of lutein provide its many protective roles in various ocular diseases especially AMD and cataracts. Lutein has become known as the “eye vitamin” and its dietary intake is important in maintaining its concentration in human lens and retina.
Overall, results scientific studies are consistent, suggesting diets and lifestyles which limit oxidative stress and inflammation are protective against early AMD, and this may be most important for reducing AMD risk in individuals at high genetic risk. This suggests interventions to consume plant-rich, high-lutein diets, reduce smoking and encourage physical activity, are reasonable strategies for AMD prevention, particularly in groups of people who are at high genetic risk and/or have a family history of AMD.