Lutein and zeaxanthin

They are sometimes called “eye vitamins” because they are known for their ability to protect the retina and other structures of the eyes. But perhaps even more important is the ability of lutein and zeaxanthin to support mental abilities and proper brain development, and they may even slow the aging process and the progression of arthritis.

Description

Lutein and zeaxanthin are plant dyes belonging to carotenoids, specifically to a group of carotenoids called xanthophylls. Lutein is yellow in low concentrations, orange-red in higher concentrations, and zeaxanthin is yellow-orange. The reason why we mention both substances together, and not in separate articles, is simple: they are not only very similar in structure (they are so-called isomers), but also in function, and they occur together in many of their sources.

Occurrence

Both lutein and zeaxanthin are produced only by plants, animals must take them in through food. The richest source is vegetables with dark green leaves. 100 g of spinach, for example, contains 12 mg of lutein, the same amount of kale even 40 mg. An egg yolk contains about 140 µg of lutein. Other sources of both substances include kiwifruit, grapes, corn, zucchini and pumpkin, curcurrants, oranges and mangoes.

For infants, breast milk is an important source of lutein and zeaxanthin, but their content varies greatly depending on the mother’s diet and other factors. In research, the highest levels of lutein and zeaxanthin were found in the breast milk of Japanese women, while women in the USA had the lowest levels. In addition, the results of some studies suggest that lutein and zeaxanthin are absorbed significantly less readily from artificial milk than from breast milk, which may be one reason for the positive effect of breastfeeding on the child’s intellect. (11)

In animal tissues, lutein and zeaxanthin are most abundant in the eyes and brain, followed by the skin, ovaries, breast tissue and uterus. During pregnancy, the most abundant carotenoids are found in the placenta and umbilical cord blood. (28, 29)

History

In 1782, the so-called macular pigment, a dye in the retina that we now know is made up of a mixture of lutein and zeaxanthin, was first described. However, its composition is still a long way from being described. The discovery of lutein is attributed to the Austrian chemist Adolf Lieben (1836-1914), who studied the pigments found in the so-called corpus luteum in the mammalian ovary. Together with his colleague G. Piccolo then isolated a red crystalline substance from the yellow corpuscles of cows, which, however, because of its red colour, he considered to be a compound derived from haemoglobin. The physician Johann Ludwig Wilhelm Thudichum, however, shortly afterwards subjected the substance to spectroscopic analysis and found that its spectrum was practically identical to that of carotene. He called it lutein and published his discovery in 1868. It was not until 1985 that the macular pigment was found to contain lutein and zeaxanthin (9, 28).

Effects of lutein and zeaxanthin

One important feature distinguishes them from other carotenoids: while beta-carotene or lycopene have non-polar molecules (no part of their molecules has a positive or negative charge), lutein and zeaxanthin have two polar groups on their non-polar chain. As a result, they can form a very functional part of cell membranes, as they are highly soluble in them, and at the same time, thanks to their polar groups, they can form a kind of “bridging”. Thus, they can positively influence the function of cell membranes, improve their stability and effectively protect them, for example, from the action of free radicals. These mechanisms are particularly applicable in brain and eye tissue (1, 3, 4).

Like other carotenoids, lutein and zeaxanthin are very powerful antioxidants that protect the body from the negative effects of free oxygen radicals. They also have strong anti-inflammatory effects, which are due to their epigenetic action – lutein in particular can reduce the production of inflammatory cytokines and proteins. Epigenetic mechanisms are also involved in its ability to protect the retina, brain tissue and articular cartilage, as well as its anti-cancer effects (34-37).

The ability of lutein and zeaxanthin to absorb the blue components of sunlight is also important for protecting the eyes and skin. In addition, both of these carotenoids help protect the body from radiation and ionizing radiation (34).

Mental abilities and brain development

Lutein and zeaxanthin play an important role in brain development during intrauterine development and early childhood. For example, when mothers were given a combination of lutein and zeaxanthin or a diet rich in these substances during the first two trimesters of pregnancy, their children subsequently showed higher intelligence (especially in the verbal domain) as well as greater ability to regulate behaviour and better social-emotional development. Interestingly, the differences in cognitive abilities did not become apparent in early childhood, but only around mid-childhood, i.e. at the beginning of schooling (9).

In infants, lutein has also been found to be the predominant carotenoid in some important brain regions, particularly the occipital cortex, auditory cortex, hippocampus and frontal lobe, areas associated not only with cognitive abilities and memory, but also vision and hearing. Although in infants lutein accounts for only 12% of total carotenoid intake, in the brain it already accounts for 59% of the carotenoids present in this tissue, compared to only 34% in adults. This suggests that lutein plays a very important role in the development of the brain and nervous system and that sufficient intake is therefore important during pregnancy and lactation as well as during childhood (10, 11).

In children, the importance of lutein has also been demonstrated at the age of 7-13 years. One study, for example, found that children who had higher levels of lutein in the retina (which usually means higher levels in the brain) performed better on tests of language and math skills, as well as comprehension and spatial imagination, and also on the so-called “lutein” test. Children with higher levels of lutein, for example, needed less attention to solve the same task (11).

However, intake of lutein and zeaxanthin is essential for maintaining optimal brain function in adulthood and especially in older age, when it slows down ageing-related processes in the brain and improves the ability of nerve cells to form interconnections. While high concentrations of zeaxanthin have also been found in the brain of adults (although slightly lower than lutein), the contribution of zeaxanthin in the brains of children has not yet been investigated in detail. Moreover, in adults, levels of both substances have been shown to be related to general intelligence, memory, learning ability, language ability, concentration and speed of task processing (11, 40).

Regarding the mechanisms by which lutein and zeaxanthin act on the brain, its ability to protect omega-3 unsaturated fatty acids from oxidation is very important. These are an integral part of cell membranes and are found in high concentrations in the membranes of nerve cells, but they are also very susceptible to oxidation by free radicals. In addition, the brain’s lutein content is closely related to the levels of several neurotransmitters, which are substances required for the transmission of nerve impulses, and also protects the brain against microglia, which are specific immune cells that release cytokines that increase inflammatory processes (12, 13, 14)

Alzheimer’s disease

The combination of the antioxidant and anti-inflammatory effects of lutein and zeaxanthin is also used to prevent and support the treatment of Alzheimer’s disease. Their combination with omega-3 unsaturated fatty acids is particularly effective here (15, 16).

Eye diseases

Even higher concentrations of lutein and zeaxanthin can be found in the eyes – both substances are found here up to 3 times more than in the brain, especially in the retina. They also have a significant protective effect on the cells: they trap and neutralize harmful free radicals, prevent lipid oxidation in cell membranes, and can even partially absorb blue light, which could be destructive to the retina to a greater extent. In addition, they have a beneficial effect on the function of the blood vessels that supply the retina and choroid with blood. In addition, epigenetic mechanisms are involved in the protection of the retina, as lutein prevents the activation of the inflammatory gene induced by linoleic acid and thus protects retinal cells from damage (19, 37).

These mechanisms are particularly effective in the prevention and treatment of age-related macular degeneration, a degenerative disease of the retina that in many cases results in complete blindness. For example, research has shown that sufficient concentrations of lutein and zeaxanthin in the blood plasma reduce the risk of developing advanced macular degeneration by 40% and slow down the progression of the disease. This protective effect is seen in various types of macular degeneration (19, 20, 23).

Adequate intake of lutein and zeaxanthin is also important in the prevention of cataracts. In this disease, the lens of the eye becomes cloudy, causing blurred vision. The cause here is mainly free radical damage to the lens, as the concentration of glutathione, which is responsible for its antioxidant protection, decreases with age. Lutein and zeaxanthin, as powerful antioxidants, are therefore seen as an alternative to declining glutathione – and lutein is also present in the lens itself. Research has shown that people with a high intake of both substances have a 50% lower risk of developing cataracts. They are particularly effective in so-called nuclear cataracts, which are cataracts that form in the central zone (nucleus) of the lens, while the effectiveness in other forms, i.e. subcapsular and cortical cataracts, is significantly lower. In one study, the use of both agents was also shown to reduce the risk of needing cataract surgery (21, 25, 40).

Another eye disease in which lutein and zeaxanthin reduce the risk and slow the progression is diabetic retinopathy, or damage to the retina due to high blood sugar in diabetics (24).

In contrast, mixed results were recorded for myopia. Although the beneficial effect of lutein and zeaxanthin on the alleviation of this eye disease has not been reliably confirmed, both substances have been shown to promote the production of hyaluronic acid in the vitreous, which is essential for optimal light refraction and may slow the progression of the disease. In addition, one study has shown that lutein and zeaxanthin can increase visual acuity and contrast sensitivity (25, 40).

So far, only two small clinical trials have investigated the use of lutein in retinitis pigmentosa, an inherited retinal disease that manifests itself as blindness, narrowing of the field of vision and impaired visual acuity, and can even lead to blindness. For example, people with this disease who took lutein for 24 weeks experienced a widening of the visual field (26)

The protective function of lutein has also been proven in premature infants at risk of retinal damage (retinopathy). In addition, these children have lower levels of lutein in their eyes (and also in their brains) than premature babies, so supplementation is very useful for them (17).

Skin protection

Both lutein and zeaxanthin can effectively protect the skin from the effects of UV radiation, both when used internally and when applied externally. When administered after UV exposure, their administration also helps to reduce skin swelling and slow cell division. They also improve skin quality and slow the rate of skin ageing – for example, when lutein and zeaxanthin were given to a group of women who also applied both nutrients directly to their skin, their skin showed an increase in oil content, improved hydration and even skin elasticity (18, 33, 40).

Tumour diseases

Both lutein and zeaxanthin have anti-cancer effects. The reason for this is both their antioxidant potential and their ability to inhibit angioneogenesis, or the formation of new blood vessels necessary to supply a growing tumor. (30)

In addition, lutein increases the activity of genes involved in protecting the body against cancer, such as P53 and Bax, through epigenetic pathways (37).

Diseases of the heart and blood vessels

Xanthophylls, including lutein and zeaxanthin, have also been linked to cardiovascular health. Their use has been shown to have a protective effect on the cardiovascular system, particularly in the setting of high blood pressure and elevated cholesterol levels. (31, 32)

Arthrosis

In the case of lutein, a positive effect in arthritis has also been confirmed. This is due not only to its antioxidant and anti-inflammatory action, but also to its ability to support the “life” of cartilage cells, thus slowing down the process of cartilage degradation. It has a positive effect on the mitochondrial membrane of cartilage cells, which reduces the rate of apoptosis or cell death. Mitochondria are essential for the function of cartilage (and indeed any other tissue in the body) – if they are not functioning properly, the cell does not have enough energy to function, which can lead to its death. However, the anti-inflammatory action mentioned above is also important for slowing down the progression of arthrosis, as inflammatory cytokines also damage the structure of cartilage (37).

Slowing down aging

Lutein can increase the production of SIRT-1, an enzyme from the sirtuin family that effectively slows the aging process. This effect is applied in the protection of the retina (for example, in the prevention of macular degeneration), but it also works across all tissues of the body. In addition, lutein suppresses the production of the enzymes collagenase and elastase, which are involved in skin ageing, but also in the degradation of joint structures (38, 39).

Use and contraindications

Lutein and zeaxanthin are generally considered safe even in long-term use. Research shows that the daily requirement of lutein for an adult is 1.4-1.9 mg, but in the case of dietary supplements, higher doses, usually 10-40 mg, are usually used. No significant negative side effects have been observed in studies using 10 mg daily for 5 years, 30 mg for 120 days and 40 mg for 9 weeks. It can also be used by pregnant women (25).

Zeaxanthin is usually taken in doses starting at 2 mg/day, but no side effects have been reported even when taken at 10 mg/day for one year. However, it may lower blood sugar levels, so use with antidiabetic drugs should be discussed with the treating physician. (6)

Lutein and zeaxanthin in a ratio of 10 : 2 is also sometimes recommended (40).

Lutein and zeaxanthin should be taken together with omega-3 unsaturated fatty acids, the most important of which is DHA. These nutrients are interdependent in their action. However, some other combinations are also suitable, for example with vitamin E or astaxanthin. (40)

Suitable combinations

Eyes: lutein + zeaxanthin + omega-3 (22), lutein + zeaxanthin + vitamin E + vitamin C + zinc (25), lutein + zeaxanthin + astaxanthin (40)

Alzheimer’s disease, cognitive performance: lutein + zeaxanthin + omega-3 (15)

Heart and blood vessels: lutein + zeaxanthin + omega-3 (32)