Can Lutein and Zeaxanthin Protect Your Eyes?

Lutein and zeaxanthin are types of compounds called carotenoids, which are pigments synthesised by plants that have antioxidant properties. Antioxidants help manage reactive oxygen species (ROS), which if left unchecked can accumulate and cause oxidative damage, leading to cell death. Beta-carotene is another example of a carotenoid, and is responsible for making carrots orange. Vitamin A, which is the light-sensitive pigment in your eyes, is also a carotenoid. Despite the name, carotenoids are found in varied food sources, such as egg yolks, spinach, kale, orange peppers, courgettes, kiwis, grapes, and squashes.

Lutein and zeaxanthin have received particular attention as antioxidants in the eye because they are by far the most prominent pigments in the retina, the part of the eye that detects light and turns it into a signal for the brain. The retina is very specific in uptaking these pigments, as other carotenoids are only present in relatively miniscule concentrations.

Antioxidants play a vital role in preserving the health of the retina. Photoreceptors, the cells in the retina that detect light, are constantly damaged and replaced by a layer of cells called the retinal pigmented epithelium. This means the retina is highly metabolically active, and as a result produces a large amount of ROS which could build up and damage cells by reacting with important cellular machinery, such as proteins, DNA, and cell membranes.

Lutein and zeaxanthin being present at high concentrations in the retina helps protect against oxidative damage, as they are known as ‘radical scavengers’ which react with and neutralise ROS. The highest density of lutein and zeaxanthin is found at the macular, which forms the centre of our vision and also has the highest density of photoreceptors. In fact, these pigments have been shown to significantly decrease progression and chance of developing age-related macular degeneration, the leading cause of blindness in the elderly. We’ll take a closer look at the eye health benefits of taking lutein and zeaxanthin later.

These pigments are also found in other parts of the eye, such as the lens, which focuses light, and the ciliary body, which provides nutrients to the inside of the eye. These parts of the eye are also susceptible to oxidative damage, but ROS are produced by exposure to UV radiation and blue light. Lutein, as well as being a potent antioxidant, absorbs blue light safely, whereas other biological molecules may produce ROS upon absorbing blue light. When some chemicals absorb blue light, they can become highly reactive, as electrons in their bonds are excited to a higher energy level. Their increased reactivity can lead to radical formation. 

However, when lutein absorbs blue light, the excited electrons relax back to a lower energy level and the energy absorbed dissipates (i.e. is spread out and becomes less intense). Blue light is higher energy than other wavelengths of visible light so it is more able to induce ROS production, and unlike UV light, blue light is not filtered out before reaching the retina. Lutein therefore serves a protective role against blue-light induced ROS too.

Lutein and zeaxanthin cannot be synthesised by our bodies and so must be obtained through our diets. Their role in the eyes is exemplified by the first sign of deficiency: night blindness (i.e. low visual acuity at night). Access to healthy and varied diets means that, in developed countries, deficiency is rarely seen, with the average American consuming 1.6mg of lutein per day. Premature infants can sometimes be critically deficient in carotenoids, and this can lead to degeneration of the retina, and the same can happen to infants breast-fed by mothers on a low Vitamin A diet. In both cases, damage can be prevented by supplementation with vitamin A, but not lutein or zeaxanthin.

For most people in developed countries, deficiency in lutein and zeaxanthin should not be a concern. However, supplementation above average daily amounts has shown promising data regarding the health of your eyes. Before analysing whether you should take supplements, we’ll first look at how lutein and zeaxanthin enter your body and how they reach the eyes.

Carotenoids are fat-soluble, which means they don’t easily mix with water. Along with the fact that carotenoids are often associated with proteins, bioavailability of lutein and zeaxanthin can vary with the food source and preparation method. For example, many vegetables are high in these carotenoids, yet eaten raw and without any other food consumed, they will only provide 2% of the lutein and zeaxanthin they contain.

In the intestines, bile secreted by the gallbladder helps emulsify hydrophobic compounds including carotenoids. Emulsification is more improved when there are higher amounts of oil and fat in the intestines, and as such lutein and zeaxanthin absorption is increased when meals are accompanied with fattier contents. They are then taken into the blood using a transporter protein called scavenger receptor class B type I (SR-BI), and incorporated into lipoproteins, which are blobs of oil used to transport hydrophobic compounds around the body.

A lipoprotein called apolipoprotein E4 (ApoE4) is responsible for directing carotenoids to the retina. ApoE4 is also involved in cell membrane synthesis, so is important in regenerating photoreceptors at the retina. When ApoE4 meets the retina, it binds to receptors that break it down, allowing the absorbance of lutein and zeaxanthin exclusive of other carotenoids. This specificity for lutein and zeaxanthin results from their chemical structure; unlike other carotenoids, lutein and zeaxanthin have additional hydroxyl groups which let them pass through the blood-retina barrier. Besides the retina, lutein and zeaxanthin are also deposited in the brain which, like the retina, is highly metabolically active and so prone to oxidative stress. 

Early clinical trials have suggested a similar protective role of lutein and zeaxanthin in the brain and may even boost cognitive function. Other carotenoids cannot pass the blood-brain barrier, but they are distributed around the body in fat cells and in the skin, where they are also thought to act as antioxidants.

Supplementation has been shown to increase retinal concentration of lutein and zeaxanthin in studies on primates and in humans. Increased pigmentation, particularly in the macula, is associated with lower risk of eye conditions such as macular degeneration, due to the increased protection against oxidative stress.

Oxidative stress is when reactive oxygen species (ROS) levels inside cells increase to levels beyond what can be managed by antioxidants (such as lutein and zeaxanthin). When this happens, cells undergo ‘oxidative stress’, where ROS react with and damage important cellular structures. 

This can lead to apoptosis, where cells die, and inflammation, where high ROS trigger signals to the immune system that leave the area irritated.

ROS are produced as a byproduct of metabolic activity, which means that parts of the body using a lot of energy are more prone to oxidative stress. The eye is an energetically demanding organ, and oxidative damage can cause conditions such as age-related macular degeneration (AMD), retinal detachment, and uveitis. 

Very little high energy radiation such as UV reaches the retina because it is absorbed by tissues at the front of the eye, such as in the cornea, lens, and ciliary body. UV can cause oxidative stress in these tissues instead, leading to conditions such as glaucoma and cataracts. Around 30% of the eye’s lutein and zeaxanthin are found in tissues other than the retina, meaning they may be vital antioxidants which protect against these diseases too. Does this mean that increasing your intake will decrease the risk of these diseases? Next, we’ll evaluate clinical evidence of lutein and zeaxanthin supplementation so you can decide for yourself.

Age-related macular degeneration (AMD) is the primary cause of age-related sight loss, and as such has been the target of many clinical trials. AMD is caused by oxidative damage to the macula, the central part of the retina and the focus of your eyesight, leading to permanent damage to photoreceptors and to the retinal pigmented epithelium, which contains cells responsible for repairing damaged photoreceptors.

The age-related eye diseases study 2 (AREDS2) studied a mixture of antioxidants and their effect on AMD development and progression. In this double-blind trial, 4,203 participants were provided with variations on the AREDS formula, containing 500mg vitamin C, 200IU vitamin E, 15mg beta-carotene, 10mg lutein, 2mg zeaxanthin, 2mg copper, and 80mg zinc, or they were given a placebo with no active ingredients. 

The study found that, whilst beta-carotene was as effective as lutein and zeaxanthin in reducing the risk of AMD, beta-carotene also increased the risk of lung cancer. However, a follow up study after 10 years on 3,882 participants found that taking the AREDS formula with lutein and zeaxanthin, but without beta-carotene, was 20% more effective in preventing AMD progression than the formula with beta-carotene lacking lutein or zeaxanthin. Furthermore, lutein and zeaxanthin did not share the increased risk in lung cancer. 

An analysis of the AREDS participants which took place over, on average, 10.2 years, looked at dietary intake of carotenoids rather than supplementation, and found a correlation between carotenoid intake and reduced risk of developing AMD. These large-scale studies provide strong evidence that increasing your dietary intake of lutein and zeaxanthin, as well as taking supplements in addition to your diet, might reduce the risk of AMD.

Diabetic retinopathy is a major cause of blindness and vision loss in the Western world, with a third of diabetics being affected. 

In diabetics, blood sugar levels cannot be controlled. Blood sugar levels can be too high, leading to increased oxidative stress, compounded by a process called glycation, in which free sugar molecules react with biological molecules similarly to how ROS cause damage at a cellular level. 

High blood glucose also activates a set of reactions in the body called the polyol pathway, producing molecules which increase glycation and cause water to flood cells so they burst. An enzyme called protein kinase C is also activated by high blood sugar, and weakens blood vessel walls. All these effects lead to damage to blood vessels which supply the retina, depriving it of oxygen and nutrients. This can cause permanent damage to the retina. 

Lutein and zeaxanthin have a major role as antioxidants in the retina, and as such have been investigated for their potential benefits in sufferers of diabetic retinopathy.

An early clinical trial on 90 participants, 60 of which suffered from diabetic retinopathy, found that those without diabetic retinopathy had a higher baseline lutein and zeaxanthin levels. Furthermore, when supplemented with lutein and zeaxanthin, sufferers saw improved visual acuity and contrast sensitivity than those provided with a placebo. Another study of similarly small scope supported these results However, these are only early studies with a limited number of participants. Whilst promising, they do not definitely prove that supplementation with lutein and zeaxanthin will improve diabetic retinopathy, or reduce its risk of development or progression. 

Uveitis is a condition in which the uvea, the middle layer of the wall of the eye, becomes inflamed, and is responsible for around 10% of the world’s blindness. Inflammation and oxidative stress are closely linked, and antioxidants have been investigated as preventatives against uveitis. 

Lutein has been shown to reduce markers of oxidative stress in the eyes of mice with uveitis. In rats with uveitis, lutein has been further shown to decrease inflammation of the uvea. It’s unclear whether the same effect could be seen in humans, and uveitis is usually treated effectively with corticosteroids in developed countries. Nevertheless, increasing intake of lutein and zeaxanthin might reduce the risk of developing uveitis in the first place.

Cataracts is the leading cause of blindness worldwide, accounting for over 50% of legal blindness. Cataracts develops when crystallins, the proteins that make up the lens, are disrupted from their well-ordered arrangement which would usually appear transparent, allowing light through to reach the retina. Instead, the crystallins clump together, making the lens cloudy and opaque. Oxidative damage to the lens is associated with cataracts as ROS react with crystallins, causing their disruption. 

Unlike in the retina, ROS generation in the lens is thought to be more caused by UV and pollutant exposure. Whilst lens lutein and zeaxanthin content is not as high as in the retina, these antioxidants are still present in the lens and as such have been investigated for their potential protective properties.

There have been some promising results. Several studies looking at peoples’ diets have found that a higher proportion of dietary lutein and zeaxanthin leads to a reduced risk of developing cataracts by as much as 50%. Another study found that increased lutein and zeaxanthin in the retina was correlated with a more transparent lens. However, these findings have not translated well to more direct studies. 

For example, one study examining both regular lenses and those suffering from cataracts found no correlation between lutein and zeaxanthin content of the lenses and whether the lenses were opaque. In the AREDS study, which examined a whole host of age-related eye diseases and whether they could be prevented by antioxidant supplementation, found no significant effect of lutein and zeaxanthin supplementation on cataracts risk. The conflicting reports from population studies on diet and studies on supplementation might suggest that having too little lutein and zeaxanthin can increase risk of developing cataracts, but beyond a certain point, increase lutein and zeaxanthin has no effect on cataracts, unlike the results we saw for AMD.

Glaucoma is the irreversible degradation of the optic nerve caused by a buildup of pressure in the eye. The ciliary body produces fluid called the aqueous humour, which provides nutrients to tissues in the front of the eye such as the lens and iris. That fluid drains through the trabecular meshwork, but oxidative damage to the trabecular meshwork makes it less porous, and so less fluid can escape, causing an increase in pressure. 

The risk of glaucoma increases with age, consistent with accumulating exposure to UV over a lifetime, and glaucoma patients consistently show reduced overall antioxidant levels, possibly due to sustained oxidative stress over long periods of time. 

The role of lutein and zeaxanthin in the rear of the eye, where the optic nerve is located, has led to an interest in their potential to slow the progression of glaucoma.

Clinical studies into treating glaucoma with lutein and zeaxanthin are limited. One study on 30 participants provided with a supplement containing several antioxidants including lutein and zeaxanthin, and found that there was a general body reduction in oxidative stress, with increased antioxidant levels, with a higher relative increase when people suffering with glaucoma took the supplement than on healthy individuals. 

Since glaucoma often leads to depleted antioxidants, this might suggest lutein and zeaxanthin could repair antioxidant systems in glaucoma patients. However, there was no placebo in this trial, and it was a very small sample size. A slightly larger study with 117 participants over two years found no difference in the progression of glaucoma in the group given antioxidants (including lutein and zeaxanthin) than those given no supplement.

Large scale studies on population dietary intake of lutein and zeaxanthin contradict these findings. The analysis of two studies, totaling over 115,000 participants, found increased dietary intake was associated with reduced risk of developing glaucoma. 

Further analysis revealed that by eating food groups high in lutein and zeaxanthin, the risk could be reduced by as much as 20%. However, this could be caused by other health benefits of eating these foods, which are generally green leafy vegetables high in nutrients. Furthermore, another study on over 3,500 over-55 year olds found no association between dietary intake of lutein and zeaxanthin and the risk of development or progression of glaucoma. 

Overall, whilst there is some evidence that dietary intake of carotenoids could slow the development and progression of glaucoma, there’s no evidence that supplementation has any effect.

Lutein and zeaxanthin are carotenoids and important antioxidants in the eye, having the highest abundance of any pigment in the retina. They are essential for neutralising the high levels of ROS produced by the highly active photoreceptor cells and retinal pigment epithelium. They are also found in other parts of the eye, such as the uvea, lens, cornea, and ciliary body, but they are not thought to be the primary antioxidants in these regions.

Studies have been carried out testing the value of lutein and zeaxanthin supplementation or dietary intake for protecting against numerous diseases. There is strong evidence that the risk of developing age-related macular degeneration (AMD) and its rate of progression can be reduced by supplementation with lutein and zeaxanthin, based on one of the largest clinical trials ever carried out: the age-related eye disease study (AREDS). Dietary intake has also been shown to be a factor.

Other diseases such as diabetic retinopathy, glaucoma, cataracts, and uveitis, have not seen the same results upon supplementation with lutein and zeaxanthin, excluding some early studies into diabetic retinopathy. However, large-scale studies on dietary intake generally support the idea that increasing lutein and zeaxanthin intake by choosing foods higher in these carotenoids, such as egg yolks, spinach, kale, orange peppers, courgettes, kiwis, grapes, and squashes, can significantly reduce the risk of developing these diseases. Whether supplementing or obtaining from your diet, lutein and zeaxanthin are more efficiently absorbed when consumed alongside fatty or oily meals, due to their hydrophobic properties.

The health benefits of lutein and zeaxanthin have quite substantial evidence. You can decide, knowing your own diet and lifestyle, whether supplementation is necessary. However, we do know that, in most cases, increasing dietary intake with a balanced diet that includes several vegetables, oils and fats, decreases your risk of developing diseases which are some of the largest contributors to blindness in the world.