«Wild Edible Plant Consumption and Age-Related Cataracts in a Rural Lebanese Elderly Population: A Case control Study By Joelle Zeitouny School of ...»
Only primates have the anatomical feature of a macula; thus it is not physically possible to study the role of carotenoids in macular degeneration in experimental animals such as rodents for example, who do not have a macula. In monkeys fed diets devoid of plant pigments for several years, levels of these pigments in the macula disappear and retinal abnormalities that resemble age-related degenerative changes in humans (drusen accumulation Figure 2.9) appear (Malinow et al., 1980).
Xanthophyll profiles in quail mimic those in primates: Quail retina, like the primate macula, is dominated by cone photoreceptors and concentrates lutein and zeaxanthin. Moreover, retinas of aged quails exhibit the characteristics of aged primate retinas including age-related loss of photoreceptors (Fite & Bengston, 1989).
Preliminary studies indicate an inverse correlation between the level of zeaxanthin in quail retina and light-induced retinal cell death (Dorey et al., 1997; Thomson et al., 2002).
There has been a substantial interest in the role of diet and nutrition in agerelated macular degeneration. A large case control study by the Eye Disease Case Control Study (EDCCS) Group compared the fasting serum samples of 615 controls to 421 patients recently diagnosed with the less common, but more severe, neovascular or wet form of age-related macular degeneration (The Eye Disease CaseControl Study Group, 1993). Those with lutein/zeaxanthin concentrations 0.67 µmol/L were 70% less likely to have age-related macular degeneration than those 22 with concentrations 0.25 µmol/L (OR: 0.3; 95% CI: 0.2–0.6; p-trend=0.0001). In a subsequent study by Seddon et al. (1994), among 356 cases and 520 controls, those in the highest quintile of carotenoid intake had a 43% lower risk of developing agerelated macular degeneration compared to those in the lowest quintile. From all the carotenoids ingested, the strongest association with protection from age-related macular degeneration was found for lutein and zeaxanthin. Subjects who were in the highest quintile for their intake of lutein and zeaxanthin had a 57% lower risk of advanced age-related macular degeneration (OR: 0.43; 95% CI: 0.2–0.7, ptrend0.001) compared to those in the lowest quintile and subjects in the highest quintile for consumption of spinach had an 86% lower odds ratio of advanced agerelated macular degeneration.
In 2001, Bone et al. obtained donor eyes from age-related macular degeneration patients and control subjects, and measured the actual concentrations of lutein and zeaxanthin in the area including and surrounding the macula. Within the area most closely surrounding the macula, those subjects possessing the highest concentration were 82% less likely to have age-related macular degeneration relative to those with the lowest concentration.
However, not all studies have found an association between serum carotenoids or macular pigment concentrations and protection from age-related macular degeneration. For example, a case-control study that used a sample of 167 casecontrol pairs selected from the population of Beaver Dam Eye Study found no such association for lutein or zeaxanthin (Mares-Perlman et al., 1995). Another study by VandenLangenberg et al. (1998) that followed subjects from the Beaver Dam cohort who were free of late stage age-related macular degeneration at baseline for five years found no significant association between specific macular lesions and lutein and zeaxanthin intake, either 10 years before study enrollment in the study or at baseline.
Similarly, a small case control study by Sanders et al. (1993) in the United Kingdom found no significant differences between the mean plasma lutein concentrations of 65 23 patients with age-related macular changes and the lutein concentrations of 65 control subjects.
On the other hand, recent studies suggest that lutein supplementation may improve visual function in age-related macular degeneration patients. Falsini et al.
(2003) evaluated the influence of short-term antioxidant supplementation of vitamin E, nicotinamide, and 15 mg/d lutein for 180 days to age-related maculopathy patients and control subjects on retinal function by recording focal electroretinograms. A significant increase in amplitude change of the focal electroretinograms was reported in patients and controls with antioxidant supplementation. However, the specific effects of any one component could not be assessed. The Lutein Antioxidant Supplementation Trial (LAST), a double-blind, randomized, placebo-controlled study, supplied 90 males with atrophic age-related macular degeneration with either 10 mg of lutein, 10 mg of lutein plus a broad spectrum formula containing antioxidants/vitamins/minerals, or placebo for one year (Richer et al., 2004). Lutein and antioxidant supplementation resulted in positive effects on visual function, including improved contrast sensitivity, glare recovery, and visual acuity (Richer et al., 2004).
Differences in the range of lutein and zeaxanthin exposures and/or the severity of age-related macular degeneration may partly explain the inconsistent findings of these results (Moeller et al., 2000). Additional epidemiologic studies that demonstrate consistency of associations across populations and further evaluate the strength of the association of dietary intake of lutein and zeaxanthin with a reduced risk of developing cataracts or age-related macular degeneration are needed. Evidence is also needed to prove that the findings are specifically due to the intake of lutein and zeaxanthin rather than other aspects of diet or lifestyle that are more common in people who eat diets rich in these carotenoids (Marles-Perlman et al., 2002). Thus, the evidence to support the possibility that lutein and zeaxanthin promote eye health is emerging but currently insufficient.
2.5.1 Other antioxidants and age-related cataracts Dietary antioxidants accumulated by the lens include not only lutein and zeaxanthin but also vitamin C and vitamin E (Taylor et al., 1991; Yeum et al., 1999).
These antioxidants along with β-carotene have been found collectively or individually to influence the risk for cataract. In fact, higher dietary or serum levels of vitamin E (Vitale et al., 1993; Leske et al., 1998; Rouhiainen et al., 1996; Mares-Perlman et al.,
2000) and vitamin C (Taylor et al., 1991, 2002; Mares-Perlman et al., 2000; Jacques et al., 2001) have been associated with a reduced risk for cataract in both crosssectional and longitudinal studies. These associations are reinforced by evidence from intervention studies which showed that cataract risk was reduced in subjects whose diet was supplemented with tocopherol (Leske et al., 1998; Mares-Perlman et al., 2000), ascorbate (Taylor et al., 1991; Mares-Perlman et al., 2000; Taylor et al., 2002) or a mixture of ascorbate, tocopherol, and β-carotene (Chylack et al., 2002).
Unfortunately, risk for cataracts has not been consistently associated with tocopherol, ascorbate, or β-carotene. As a matter of fact, the Age-related Eye Disease Study, a prospective study of 4629 subjects, found no reduction in the 7-year risk for age-related cataracts of any type in those given multivitamins or supplemental ascorbate, tocopherol, β-carotene and zinc (Age-Related Eye Disease Study Group, 2001). Neither plasma ascorbate nor β-carotene influenced cataract risk in the Baltimore Longitudinal Study on Aging (Vitale et al., 1993) and plasma tocopherol was not associated with risk for cataracts in England (Gale et al., 2001), or lens optical density in the Netherlands (Berendschot et al., 2002). Moreover, tocopherol supplements had no effect on the incidence of cataracts or rate of cataract extraction in Australia (McNeil et al., 2004) or on the prevalence of cataracts in middle-aged Finnish smokers (Teikari et al., 1997).
25 On the other hand, higher dietary levels of certain carotenoids such as carotenes and lycopene, which are not present in the human lens, were associated with reduced risk for cataracts in several studies (Yeum et al., 1995; Bates et al., 1996; Bernstein et al., 2001). As a matter of fact, intakes of α-carotene, β-carotene, and total carotenoids were related to risk for posterior subcapsular cataracts in American women (Taylor et al., 2002) and higher plasma concentrations of lycopene, and α- or β-carotene were respectively associated with a reduced risk for cortical and nuclear cataracts in English subjects (Gale et al., 2001). In addition, β-carotene supplements were found to reduce excessive risk for cataracts among smokers by ≈ 25% (Christen et al., 2003) and supplementation with a mixture of β-carotene and vitamin E significantly slowed the increase in density of cataractous lenses of American subjects (Chylack et al., 2002). Nonetheless, β-carotene and vitamin E had no effect on lens optical density of English subjects (Chylack et al., 2002) or on risk of cortical, nuclear or posterior subcapsular cataracts in Finnish smokers (Teikari et al., 1997).
2.5.2 Other antioxidants and age-related macular degeneration
As with cataracts, there is a substantial body of evidence on diet and agerelated macular degeneration but no consistent findings to support a protective role for dietary antioxidants other than lutein and zeaxanthin in delaying age-related macular degeneration. Case control and population-based studies suggest, however, that important associations do exist between micronutrients with antioxidant properties and age-related macular degeneration.
In fact, the most compelling of these associations were found in the Eye Diseases Case Control Study (1993) where there was a progressive decrease in the risk of age-related macular degeneration with increasing serum levels of carotenoids and increasing antioxidant index (a composite score based on serum carotenoids, selenium, vitamins C and E). Similarly, in the Baltimore Longitudinal Study of aging, high levels of plasma α-tocopherol or a high antioxidant index (constructed from 26 plasma ascorbic acid, α-tocopherol, and β-carotene) were protective for age-related macular degeneration (West et al., 1994). In the National Health and Nutrition Examination Survey, which was one of the first studies to evaluate the role of nutrition in ophthalmic disorders, the frequency of fruits and vegetables rich in vitamin A consumed was negatively correlated with age-related macular degeneration (Goldberg et al., 1988). In addition, interestingly enough, subjects who were in the lowest quintile for serum lycopene were twice as likely to have either wet or dry agerelated macular degeneration in the Beaver Dam Eye Study (Mares-Perlman et al., 1995a). More recent small studies also observed positive associations between agerelated macular degeneration status and serum vitamin E (Belda et al., 1999) or dietary intakes of antioxidants (Snellen et al., 2002).
On the other hand, no association was found between age-related macular degeneration and serum β-carotene, serum α-tocopherol, dietary antioxidants, or oral zinc in the Blue Mountain Eye Study (Smith et al., 1997; Flood et al., 2002). On the contrary, quite surprisingly, increased serum vitamin C was associated with an increased risk for age-related macular degeneration (Flood et al., 2002). No significant associations between vitamin supplementation and risk of age-related macular degeneration were found either in the large Physicians Health Study I (Christen et al., 1999), and in the POLA study, plasma tocopherol levels were only weakly negatively associated with age-related macular degeneration (Delcourt et al., 1999). It is also noteworthy to mention that even though a trial by Newsome et al.
(1988) showed that zinc-treated subjects had significantly less visual loss than the placebo group after a follow-up of 24 months, a subsequent trial by Stur et al. (1996) using a similar study design has failed to substantiate these findings.
The above-mentioned case control and population-based studies have raised intriguing hypotheses and have thus provided the basis for the multiple interventional studies that have been carried out. AREDS, the largest and most robust randomized controlled trial concerning supplements to date, found a significant reduction in the rate of progression of age-related macular disease with the use of a multivitaminmultimineral combination supplement made of the vitamins C and E, ß-carotene, and zinc (Age-Related Eye Disease Study Research Group, 2001a) but the results of other trials with these antioxidants and age-related macular degeneration were disappointing. A small trial by Kaiser et al. (1995) investigated the effect of Visaline (vitamin C, vitamin E, β-carotene, and buphenine) on the progression of age-related macular degeneration and failed to show significant differences in any of the parameters measured. Likewise, the Vitamin E intervention in the Cataract and Agerelated macular degeneration Trial (VECAT) concluded that daily supplementation with 500 IU of vitamin E does not prevent the development or progression of agerelated macular degeneration (Tikellis et al., 1999). Moreover, the α-tocopherol βcarotene (ATBC) trial, a population-based controlled study examining the effect of long-term supplementation with vitamin E and β-carotene on age-related macular degeneration status, found no statistically significant differences between those who were receiving the supplements and those who were not (Teikari et al., 1998).
2.6 STUDY RATIONALE
Cataract is one of the major causes of blindness throughout the world (WHO, 2004). In the US, the prevalence of cataract increases from around 5% at age 65 to around 40% for persons older than 75 (Klein et al., 1992). In less developed countries like for example India (Chandrashekhar et al., 2007), China (Xu et al., 2006) or Kenya (Mathenge et al., 2007), cataracts are more common and develop earlier in life than in more developed countries.