The role of antioxidants in menopause
Menopause, a form of reproductive aging, is defined as the permanent cessation of ovarian follicular activity and eventually, the menstrual cycle.
The eye is rich in nutrients and other dietary components that support and complement each other. Some nutrients are necessary for the basic physical structure of the eye, some for the physiology of sight, and others for protection. Nutrients within the visual system can be thought of as a hierarchy representing a complex of interacting factors: while vitamin A (retinol) is essential for the formation of visual pigments, the antioxidants vitamin E, vitamin C, lutein and zeaxanthin help to protect the lens and retina against light-induced oxidative damage, and the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) enriches neural tissues including the photoreceptor cells. These nutrients are known to be important for visual development early in life, starting from the fetus through infancy to early childhood. Visual acuity gradually improves until about age four, when it is comparable to that of adults. For adults a sufficient intake of these nutrients is needed throughout the lifespan to maintain visual performance, such as the ability to adapt to low light, recover from intense light and distinguish objects from their background.
The retina – the light-sensitive inner lining tissue of the eye where light energy (photons) is converted into electro-chemical signals that are sent to the brain – is a principal target tissue for vitamin A, specifically the cells where the visual pigment rhodopsin is synthesized. This pigment is essential for the process of capturing light and converting it from an external physical to an internal biological signal. The retina is rich in polyunsaturated fatty acids, which are – as part of the membranes of photoreceptors – extremely susceptible to oxidative damage. Antioxidants such as vitamin E and vitamin C can help protect the important membrane components. The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) themselves seem to perform multiple tasks supporting eye health, such as modulating gene expression and the differentiation of retinal cells. In addition, the antioxidant carotenoids lutein and zeaxanthin are thought to protect the retina and support vision through filtering the damaging wavelengths of UV light. This underscores the importance of adequate intakes of micronutrients from the beginning of life on.
One of the target tissues for vitamin A (retinol) is the retina, specifically the cells of the retinal pigment epithelium (RPE) where the visual pigment rhodopsin is synthesized. Each RPE cell has about 50,000 cell surface receptors for retinol binding protein, the carrier of vitamin A in plasma (1). The eyes and the optic nerve begin to develop in the first trimester of pregnancy, and the fetus is able to open its eyes and detect light in the third trimester. Vitamin A is essential for proper development of these tissues, and ocular malformations are one of the well-documented consequences of vitamin A deficiency during pregnancy (2). Chronic deficiency of vitamin A for people of any age can eventually cause loss of sight, but children are most vulnerable because their bodies have not had time to build up vitamin A stores. With prolonged deficiency, ocular damage progresses through stages characterized by corneal lesions and other symptoms, collectively called xerophthalmia (3). Vitamin A deficiency is the leading cause of preventable blindness in children worldwide and is a public health problem in more than half of all countries, especially Africa and Southeast Asia. For pregnant women in high-risk areas, vitamin A deficiency is prevalent during the last trimester when demand by both the unborn child and the mother is highest. In many industrialized countries, too, the average daily intake of vitamin A, preformed or as provitamin A (e.g., beta-carotene), among women of childbearing age is below the recommended intake.
The retina is extremely susceptible to oxidative damage due to its high metabolic activity, especially early in life. As a person ages, the lens of the eye begins to yellow and is able to filter some of the more damaging wavelengths of UV light (short wave or blue light). At birth, however, the lens is relatively transparent and unable to filter short wave light, leaving the retina vulnerable to light-induced oxidative damage (4). Evidence suggests that extensive oxidative damage to the infant retina occurs during the first three years of life, underscoring the importance of adequate antioxidant nutrition in neonatal eye health. This vulnerability is thought to persist until about twelve years of age. Antioxidant vitamin E protects the polyunsaturated fatty acids in the membranes of photoreceptors and is regenerated by vitamin C. Vitamin E is not more highly concentrated in the eye than in other organs, but a higher intake of vitamin E can increase retinal concentrations, which is important since this tissue is rich in polyunsaturated fatty acids (5).
The carotenoids lutein and zeaxanthin are relevant to infant visual development because of their high concentration in the macula and their antioxidant potential in protecting that tissue. Dietary lutein and zeaxanthin are absorbed in the gut and transported on lipoproteins to target tissues, most strikingly the macula of the eye. While other body tissues absorb a whole spectrum of carotenoids from the diet, the macula stores mainly lutein and zeaxanthin (6). Within the macula, lutein and zeaxanthin are most concentrated in the fovea. This tiny area in the center of the macula comprises less than 3 percent of the retina, yet it processes most of the information about fine detail that is sent to the brain (7). Evidence suggests that lutein and zeaxanthin may protect the retina and support vision by providing antioxidant protection, filtering the damaging wavelengths of UV light, and possibly supporting central vision processing in the brain. Maternal blood levels of lutein and zeaxanthin rise during pregnancy more than other carotenoids, perhaps to support mobilization of these nutrients to meet the high demands of fetal eye and neural development. Vitamin E, lutein and zeaxanthin cross the placenta in increasing concentrations in the third trimester, preparing the fetus for transition into an oxygen environment. Since preterm infants are deprived of some portion of this important intrauterine development, they are at increased risk for relative deficiencies of antioxidants (8). These deficiencies set the stage for increased oxidative damage to the retina, a condition known as retinopathy of prematurity or ROP, which can lead to blindness. In addition to being concentrated in eye tissues, lutein and zeaxanthin are the dominant carotenoids in the frontal and occipital lobes of the brain. The occipital lobe contains the primary visual cortex – the area responsible for initiating translation of neural signals into sight (9). There is at present no official recommendation for intake of lutein and zeaxanthin. However, it is known that dietary intakes of lutein and zeaxanthin in America are generally low, and this is especially true among women of childbearing age (10).
The long-chain omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are of special interest as related to eye health. Like lutein, DHA is highly concentrated in the brain and the retinal cell membranes. DHA is highly concentrated in the outer segment membranes of rod cells (responsible for black and white vision and vision at very low light levels) and cone cells (enable perception of color and fine detail in more intense light). Here, DHA modulates retinal cell gene expression, signal transduction, cell differentiation and cell survival (11). These membranes are continually being renewed in the visual process. Specialized retinal cells are capable of recycling DHA for the formation of newly produced photoreceptor cells. Even with this high level of DHA conservation, however, there is a net loss of DHA which must be replenished by the diet (12). The multiple tasks of DHA and EPA in supporting healthy vision have been well documented in humans (13). Significant scientific agreement regarding the association of omega-3 fatty acids, and DHA in particular, on visual health in adults has been documented by organizations such as the European Food Safety Authority (14) and the US Institute of Medicine (15).
DHA and an important long-chain omega-6 fatty acid, arachidonic acid (AA), are transferred from mother to fetus during gestation via the placenta and from mother to infant via breast milk. They are incorporated into the phospholipid membranes of the retina and brain and continue to accumulate during the first two years of life (16). Results from a meta-analysis of 19 studies involving preterm and term infants indicated a significant benefit of long-chain polyunsaturated fatty acid supplementation on infant visual acuity at 2, 4, and 12 months of age (17). In one study, DHA/AA supplemented formula resulted in an improvement in visual acuity at one year of age (18). Consuming preformed sources of DHA and EPA is recommended (19) and is especially important during pregnancy and lactation for infant brain and eye development. During this phase women should eat 8 to 12 ounces of seafood per week to provide an average of 250 mg of DHA and EPA per day. In contrast, according to data from a US Nutrition Survey, US women aged 20 to 49 currently consume only about 90 mg per day of DHA and EPA (10).
Vitamin A (retinol) is required for the synthesis of photopigments. The photopigment rhodopsin is synthesized in the rods and is responsible for vision under low levels of light. When dietary sources of vitamin A are inadequate for a long period of time, the amount of visual pigment in the photoreceptors declines. In the rods, reduced synthesis of rhodopsin translates into reduced ability to see in dim light causing night blindness (2, 20). During daylight the impairment is not as evident because there is usually enough light to stimulate any visual pigments that remain within the cones in the fovea, a tiny area in the center of the macula, responsible for processing the majority of visual information.
The two principal functions of lutein and zeaxanthin, which along with meso-zeaxanthin form the macular pigment, are thought to be antioxidant protection and filtering of blue light, the most damaging wavelengths of the visible spectrum (21). These properties in the retina suggest that they may enhance visual performance by acting as accessory photopigments and reducing sensitivity to glare, increasing visual range, decreasing visual fatigue, and enhancing chromatic contrast so that objects can be better distinguished from their background, thereby improving clarity of vision. Scientific studies have demonstrated that lutein and zeaxanthin do measurably improve these aspects of visual performance. In addition, there is reason to believe that lutein and zeaxanthin have beneficial effects on temporal processing speed – the brain’s ability to process visual information.
Glare discomfort is an adverse reaction to intense light, which causes a chemical change in the visual pigments of the photoreceptors. Rhodopsin molecules in the photoreceptors must be regenerated before they can respond to further stimulation. This takes some time and contributes to the phenomenon of seeing an afterimage following a flash of bright light, as from a flashbulb. Glare disability or photostress refers to a reaction so severe that one is momentarily blinded. Intense light also tends to scatter within the eye due to irregularities in the lens, which accumulate with age. Retinal lutein and zeaxanthin have the capacity to absorb this scattered intraocular light, thereby reducing both the intensity of discomfort and the time required for recovery under such conditions. A study in 40 healthy young participants found a strong relationship between the ability to withstand discomfort from scattered light in the eye and the ability to recover from a blinding light exposure. The participants were then supplemented for six months with 10 mg of lutein and 2 mg of zeaxanthin, which raised their macular pigment levels (measured as macular pigment optical density or MPOD), improved their glare disability (how much light they could withstand and still see) by 58%, and improved their visual recovery time by on average five seconds (22). During night driving five seconds would translate to 440 feet (135 m) of distance at 60 mph. The strong relationship between serum lutein and zeaxanthin concentrations, MPOD and immediate effects on visual function, including photostress recovery and glare disability, was confirmed in a recent study of 150 healthy young participants (23).
Working for long hours at visually demanding tasks, such as at a computer, leads to visual fatigue and discomfort. Several studies have suggested benefits on visual fatigue from supplementation with lutein and zeaxanthin. Studies in which healthy participants had to complete rigorous two-hour proof-reading test sessions (24) or were exposed long-term to computer display light (25) showed significantly reduced symptoms of visual fatigue and speeded recovery after a supplementation with lutein (12 mg/day) for 12 weeks.
The sky is blue because short-wave blue light is more easily scattered by particles in the atmosphere; blue light scatter makes distant objects appear hazy or haloed. The yellow pigments of the macula tend to absorb the blue haze more than the object, thereby increasing definition of the object. Scientists have calculated that a subject with high levels of lutein and zeaxanthin in the retina can see about 30% farther than a subject with low levels (26). Empirical evidence of this effect of improved distance vision was found in a recent experiment in healthy young subjects (27).
The ability to detect objects in the environment depends on the ability to perceive edges that delineate an object against its background. By preferentially absorbing light in the blue to green portion of the visible spectrum, the macular pigments may enhance chromatic contrast, making it easier to see, for example, a red apple against a background of green leaves. Studies in both older subjects and young subjects found that those with higher amounts of lutein and zeaxanthin and higher MPOD were better able to detect a central yellow target surrounded by a blue background (28, 29). Better chromatic contrast vision was also related to higher serum levels of lutein and zeaxanthin and higher macular pigment optical density (MPOD) in a study with young healthy subjects (23). Chromatic contrast sensitivity becomes especially important under low light conditions. Data from a small clinical trial suggest that a daily supplementation with 20 mg lutein plus 20 mg zeaxanthin can reduce light scatter by about 30% and improve the ability to see clearly in dim light (30). A study with 121 healthy participants found that supplementation with 12 mg lutein and 1 mg zeaxanthin daily for one year significantly raised central MPOD overall. When individuals in the supplemented group were analyzed according to amount of macular pigments, there were significant differences between the lowest and highest subgroups in contrast sensitivity under dim light conditions, contrast sensitivity under dim light with high glare conditions, and light/dark adaptation (31).
Lutein and zeaxanthin make up about 66% to 77% of the total carotenoids in the frontal and occipital lobes of the brain, the areas that control visual processing (30). There is evidence that higher macular pigment is related to a higher temporal processing speed of visual stimuli (32, 33) and to visuo-motor function (34). Concentrations of lutein in the retina are highly correlated with concentrations of lutein in the brain, especially the cerebellum, the region that controls fine muscle movement and coordination (35). Researchers hypothesize that faster vision enabling faster reaction time could translate to meaningful advantages in sports such as baseball, where milliseconds can make the difference between a strike and a home run (36).
Astaxanthin, a red carotenoid found in marine sources such as algae, red yeast and seafood (crab, crayfish, lobster, shrimp, salmon, trout), has been found to be a powerful antioxidant with unique cell membrane actions and a multitude of potential health benefits. Several trials investigated the effects of astaxanthin on vision and eye strain. In one trial, 6 mg per day of supplemental astaxanthin improved visual acuity (37). In another, 5 mg per day of astaxanthin significantly relieved eye strain in middle-aged subjects working at computer terminals (38). Two trials showed improvements in distance vision from astaxanthin supplements (38) and one showed improvements in near vision among older subjects taking 6 mg per day of astaxanthin for four weeks (37).
There has been little research in humans on the benefits of omega-3 fatty acids in visual acuity beyond infancy and early life. Based on animal research showing positive effects of docosahexaenoic acid (DHA) on visual function, researchers found that feeding DHA-supplemented bread was useful in increasing the uncorrected visual acuity in young patients with nearsightedness (myopia) (39). Another study in healthy older adults found that 90 days of supplementation with DHA significantly improved visual acuity in those participants with corrected vision, in comparison to the placebo group (40).
Menopause, a form of reproductive aging, is defined as the permanent cessation of ovarian follicular activity and eventually, the menstrual cycle.