Heartfelt Radiance: Unlocking the Power of Lutein and Zeaxanthin for Heart, Eye, and Skin Wellness

Green leafy vegetables, including spinach, cabbage, kale, cereals, and egg yolk, are rich sources of lutein and zeaxanthin, essential carotenoids found in various human body tissues. The body relies on dietary intake and supplements for these compounds, as it cannot synthesize them internally. Lutein plays a crucial role in ocular health by filtering high-energy visible waves, such as blue light, and reducing blue light by 40%. Its antioxidant properties aid in preventing cataracts and age-related macular degeneration (AMD) by neutralizing free oxygen radicals. Additionally, lutein enhances the optical density of macular pigments, improving contrast. Studies have shown that a daily lutein supplement of 12 grams over 12 months enhances vision quality, positively impacting myopia by stimulating hyaluronic acid production.

In both adult and infant brains, lutein is the dominant carotenoid, capable of crossing the blood-brain barrier. Its positive effects on cognition stem from its antioxidant and anti-inflammatory properties, integrating with cell membranes. Higher levels of lutein, choline, and docosahexaenoic acid strengthen recognition memory in infants. Observational studies suggest that increased lutein intake may reduce the risk of Alzheimer's disease. 

Lutein exhibits a dominant cardioprotective function, offering potential treatments for myocardial infarction and preventing angiotensin II-induced cardiac remodeling. It safeguards the heart from doxorubicin-induced toxicity, alleviates oxidative stress, and improves glucose intolerance. In skin health, lutein demonstrates protective effects against blue wavelengths, preventing various skin diseases. Its supplementation enhances skin appearance, attenuates inflammatory responses, and inhibits pro-inflammatory gene expression. Recent studies highlight the benefits of both topical and oral lutein types, individually reducing lipid peroxidation, increasing skin elasticity, surface lipid, and hydration. The combined use of oral and topical applications amplifies these effects, emphasizing the multifaceted role of lutein in promoting overall health.

Lutein is a carotenoid with two oxygen atoms in its structure and is found in green leafy vegetables such as spinach, cabbage, Kale, cereals, and egg yolk [1]. Although the amount of xanthophyll in poultry eggs is not comparable with the results of leafy vegetables, the evidence shows that Poultry egg xanthophylls are more bioavailable [2].

these are lipophilic pigments that have a role in different colors in plants, Classification of carotenoids:

1. Provitamin A. 1 is converted to vitamin A 
2. Non-provitamin A cannot be converted into vitamin A (lutein and zeaxanthin are also part of this category known as xanthophyll). Xanthophyll has significant structural similarity with other carotenoids (such as beta-carotene). Still, the free hydroxyl groups in The ends of the molecule give it unique bio-properties such as Xanthophylls can be directed inside the cell membrane and lipoproteins [3] Zeaxanthin is a symbiotic isomer of lutein carotenoids are also present in different human body tissues; the human body cannot make lutein and must obtain it through food or supplements. For this reason, lutein intake greatly depends on people's diet and eating habits [4].

According to research evidence during which 60 grams of spinach were added to the diet of 11 people daily for 15 weeks, which is equivalent to 11 grams of lutein per day, the result was that in most of these people, the amount of lutein in the blood and macular pigments (lutein and zeaxanthin) has increased. This shows that, firstly, it is possible to increase the amount of lutein through food, and secondly, we can quickly increase the level of lutein in our body with a slight change in our diet [5, 6].

Known actions of lutein and zeaxanthin:

Protecting the macula lutea from the damaging effects of intense light and reduction of cataracts and AMD. The filter of extreme wavelengths from the spectrum of visible light. Antioxidant against reactive oxygen substances and free radicals the prevention of heart diseases and heart attacks decrease the risk of cancers, especially breast cancer animal studies have also demonstrated a protective effect on the skin against UV rays [7-9].

Lutine and eye health

Perhaps it is better first to know the mechanism of light entering the eye and image formation. 

Light path: cornea to aqueous humor to the lens and the rays are focused by the lens and then to the vitreous and finally hitting the pupil

The presence of cones and cylindrical cells in the pupil transmits light energy in the form of impulses to the brain through the optic nerve.

The cornea and the lens are two structures that filter and concentrate light rays of different wavelengths. The cornea can pass UV waves, while the eye's lens is responsible for preventing the entry of UV waves.

The lens removes UV waves, and the rest of the light waves are focused on the retina, so almost exclusively visible light is focused on the retina.

The proteins of the eye's lens may be oxidized and cause the opacity of the lens and its transparency, which we refer to as cataracts.

Visible light can also cause damage to cells, especially if it has a shorter wavelength, which naturally has more energy; From the visible spectrum, blue light as a high-energy visible light is more than 100 times more effective than red light as a low-energy visible light in creating free radicals in retinal cells.

Macula lutea: a part of the retina on which the lens focuses the transmitted light (focal center), contains the most photoreceptors and therefore is responsible for the central sense of vision and is effective in increasing visual acuity and increasing resolution(figure 1) [10].

Figure 1: Optic disk Components

The cylindrical or rod cell of the retina (photoreceptor) has three parts (figure 2).

1. Outer segment 

2. Inner segment

3. Synaptic terminal [11].

One of the places of lutein in the body is eye tissue. The distribution of lutein in the eye is not the same. In fact, in the lens and retina of the eye (especially in its central part called the macula), lutein accumulation is higher than in other places, and this type of dispersion seems logical with the functions of lutein and the benefits it has for the eye. Among the other carotenoids inside the macula is meso-zeaxanthin, which has a structure related to lutein but is not found in the bloodstream. They believe that meso-zeaxanthin is a photochemical substance resulting from the transformation of lutein. These pigments act as antioxidants against free radicals produced by photoreceptors and protect them. In addition, these pigments filter high-energy visible waves such as blue light and reduce blue light by 40%. They enter the macula lutea. In this way, the oxidative stress that blue light on the retina may cause is reduced [10]. It is essential to know that the presence of xanthophylls in the tissue of the eye, or better to say, the macula lutea (in the form of exclusive and selective deposition), is ultimately the result of their presence in the diet [12].

One of the roles of lutein is preventing and treating some eye diseases. such as cataract disease and AMD disease (age-related macular degeneration)  in cataract disease, the eye's lens becomes cloudy and creates an obstacle to the passage of light [13, 14]. This lens opacity is caused by oxidation in the lens structure. So antioxidants can be beneficial for us in dealing with this disease [15]. The presence of lutein and its isomer zeaxanthin, which play an antioxidant role, can prevent the creation of free oxygen radicals and destroy them [16]. The placement of lutein and its isomer zeaxanthin in the lens is such that it contributes to its antioxidant function in such a way that 74% of the lutein and zeaxanthin in the lens is located in its cortical area, where it is more exposed to oxygen [4, 16]. There is evidence that lutein plays a role in preventing cataracts by inhibiting the proliferation and migration of lens cells. In a series of studies, people in the top third of the population in terms of plasma lutein concentration had a 42% lower risk of developing cataracts than those in the bottom third of the population [17]. Similarly, the research done by Brown et al. on men found that people with the highest one-fifth of lutein and zeaxanthin consumption have a 19% lower risk of cataracts than the lowest one-fifth, as well as people with higher lutein consumption during surgery. They experience a lower risk of cataract surgery [18]. We know that the types of cataracts include  (Nuclear, Cortical, and Subcapsular) [19] Jacques et al.'s study reveals that the outbreak of nuclear and premature lens opacity in people who have a very high intake of lutein + xanthine is lower than in people who have a deficient intake [20] . Taylor et al. did not find a relationship between dietary intake of lutein + xanthine with the chance of premature cortical and posterior subcapsular [21], and Lyle et al. found that long-term consumption of lutein had more potent effects on nuclear cataracts than short-term consumption and this show effect of diet on the biochemical events that cause lens opacity. An example of this was the consumption of spinach and eggs, which reduced the risk of nuclear cataracts [22].

AMD disease

It is the cause of blindness at 65 and above in the western world.

AMD disease is divided into two types based on its severity:

1. Early type or Dry
2. Late type or Wet

AMD risk factors: age - smoking – the light color of the iris - sunlight - malnutrition or poor diet – genetics, The incidence of AMD is higher in women [23, 24]. studies showed an inverse relationship between the number of carotenoids in the consumed diet and blood serum about AMD. (The higher the level of these materials, the lower the AMD) researchers showed that lutein and xanthine are the only carotenoids in the blood that can be seen in the macula [25]. Because the progression of AMD symptoms is long, it was challenging to consider a definite relationship between the risk of AMD and the consumption of Lutein and xanthine. Therefore, the researchers used the MPOD index or macular photopigment density, which is the size of the xanthophylls of the macula lutea. This index is easy to measure and is considered a protective marker for AMD [22]. In 2001, a study was conducted on the relationship between the amount of lutein and xanthine in the central area of the pupil (the macula and its surrounding tissue). In this study, these compounds were measured in two groups. One of the eyes of AMD sufferers after their death and the other of the control group found that people with the highest amount of xanthophylls were less affected by AMD. Studies with placebo-controlled intervention showed that receiving more of these xanthophylls increased their serum levels. And the level of MPOD, thus showing the protective role of these substances against AMD [26, 27].

Bernstein et al.'s study: the level of MPOD in AMD patients was about 32% lower than that of people without AMD [28]. AMD disease damages the resolution and visual acuity or VA, and a clinical study, showed a 92% improvement in visual acuity in AMD patients (whose diet contained 5 ounces of spinach (containing 14 mg of lutein) or foods containing lutein and xanthine taken 4 to 7 times a week for a year) Seddon et al.'s study: the diet with the highest intake of lutein and xanthine reduces the risk of developing neovascular AMD (OR: 0.43, 95%, CI: 0.2-0.7, P trend less than 0.001) If the frequency of collard greens and spinach consumption is more than five times a week, compared to ones who consume less than one time a month, the chance of developing AMD is lower (OD: 0.14, 95%, CI: 0.01). -1.2, P value less than 0.001 [24]. In another study, this improvement effect was investigated in AMD patients, and those who took vitamin supplements and an antioxidant cocktail containing 15 mg of lutein and xanthine every day for 18 months saw a two-fold improvement compared to those who did not. who took a placebo without lutein and xanthine [29]. Mares-Perlman et al.'s study: in 8222 people over 40 years of age - people with the highest intake compared to those with the lowest intake of lutein + xanthine ---> OR: 0.1 for pigment abnormalities (one of the early signs of maculopathy) (OR: 0.1, 95% CI: 0.1-0.3, 95%) - The highest consumption of lutein + xanthine was associated with the lowest chance of developing AMD (OR: 0.1, 95%, CI: 0.0-0.9) [30]. Richter et al.'s study: lutein consumption alone or with other foods compared to placebo consumption: increases MPOD and improves visual performance (visual acuity, contrast sensitivity, and Amsler grid index)-Amsler Index: It shows the scotoma involving the optical center due to macular problems or optic nerve problems [31].

The 2004 study had two groups

The first group consumed 10 mg of refined lutein with approximately 0.3 mg of zeaxanthin with or without antioxidants.  The second group was the control group that did not consume food containing lutein and xanthine.

The study was carried out in a double-blind method and showed that the consumption of these xanthophylls with or without antioxidants led to a 50% improvement in MPOD and a significant improvement in the parameters of visual function, contrast sensitivity, and visual acuity [32]. The blue light which emitted from electronic devices such as mobile phones, computers, televisions, and LED lamps has a short wavelength and, therefore, much energy. This light can damage the eyes by affecting them, so it should not enter human eyes in large amounts. Lutein will help us in this work. Lutein can filter blue light [33]. This feature protects the retina [4]. For this reason, people exposed to screen light for a long time are advised to include foods containing lutein in their diet [26]. 

 Increasing the optical density of macular pigments is one of the effects of lutein, which improves contrast (1.4). According to the experiments, receiving a Luthien supplement for 12 months and 12 grams daily increases the contrast and quality of vision [6]. The outer segment of retinal rod cells, which contains both lutein and zeaxanthin, contains more long-chain unsaturated fatty acids and more oxidation; adding zeaxanthin or lutein to retinal pigmented epithelial cells that were exposed to 40% oxygen and in the outer segment of photoreceptors caused a decrease in lipofuscin. (Lipofuscin is a type of yellow-brown pigment that is a lipid or fat pigment in damaged or old cells) [11]. In the quails that received zeaxanthin supplements, it was observed that the rate of apoptosis of rod and cone cells has an inverse relationship with the concentration of zeaxanthin [34].

Lutein also positively affects the eyes in dealing with myopia [35]. In this disease, the focus of the rays entering the eyeball is in front of the retina, which causes the image of distant objects to be formed in front of the retina. Research conducted on a guinea pig shows that injectable hyaluronic acid and increasing the amount of hyaluronic acid in the eye prevent the development of myopia [36]. One effect of lutein on the eyes is stimulating the production of hyaluronic acid [5]. Another effect that lutein has on the eyes is the effect on the development of the eye structure. The baby that is born must be given enough lutein to complete the development of the baby's eye structures, and this case proves the importance of lutein in the mother's milk [6]. Experiments show that if we measure two babies born, we will see that the level of serum lutein in these two babies is the same at birth. But if we feed one of them with formula and the other with breast milk, we will see that after one month, the amount of serum lutein in the baby who was fed with breast milk is higher than the level of lutein compared to the other baby [37]. Another proof that we can see of the effect of lutein or its isomer zeaxanthin on the development of the eye structure is that in the research they did on monkeys, they found out that the monkeys whose diet contains xanthophylls (lutein, zeaxanthin, etc.) were not taken, there were no macular pigments. But in monkeys that had a standard diet, this defect did not exist [38].

Lutine and brain function

Lutein is selectively collected in the area of ​​the macula lutea and is the dominant carotenoid in the brain of adults and infants. Also, Lutein can cross the BBB and enter the brain and is the predominant carotenoid of the brain, and has a critical role in brain health and cognitive function.

• The concentration of lutein in the retina is related to its concentration in some regions of the brain; Carotenoids increase gap junction communication and improve light processing in the pupil and the Correct functioning of neural circuits in the visual system
• There is a positive relationship between the high level of plasma lutein (+ carotenoid-rich diet), healthy cognitive status and function, mild cognitive impairment, and Alzheimer's.
• There is a positive relationship between MPOD and cognitive performance. The higher the amount of zeaxanthin or lutein, the better the health and mental activity

The beneficial effect of lutein is more due to its antioxidant and anti-inflammatory properties, and its ability to integrate the cell membrane as a result of increasing the stability of the cell membrane with its impact on its structure [39].  The evolutionary origin of the brain and eye is expected in the Neural Tube. Both organs have large amounts of unsaturated fatty acids and many metabolic activities, making them sensitive to oxidative substances and free radicals. 

We have two kinds of description for cognitions.

• Cognition: the mental process that we use to acquire knowledge and understand
• Cognition is a multi-dimensional concept divided into different parts, including memory, attention, language, and information processing. Cognitive domains are influenced by factors such as sleep, mood, stress, and diet, and with age, parts of this domain change (such as a decrease in processing speed, episodic memory, working memory, and executive function). They can be caused by physiological damage caused by oxidative and inflammatory factors and other factors, and lutein, with its antioxidant and anti-inflammatory role, prevents the disease mentioned above [40-42] - 2004, research by Kraft et al.:

It was about antioxidants in the adult brain 16 carotenoids, retinol, and three tocopherols were identified in the brain Xanthophylls such as lutein, zeaxanthin, and cryptoxanthin make up 66 to 77% of brain carotenoids.

The data of previous research said that 40% of total blood carotenoids are composed of xanthophyll [43].

In 2013, Johnson et al.'s study:

Measurement of blood serum and brain carotenoid levels in 42 dead people Carotenes (alpha and beta carotene, lycopene) are the dominant carotenoids in the serum (57% of all carotenoids). Xanthophylls (lutein, zeaxanthin, and cryptoxanthin) are the predominant carotenoids in the brain (72% of all carotenoids). Lutein is the most carotenoid in the brain (one-third or 34%) with a significant ratio (p<0>

Similarly, it confirmed the preferential absorption of lutein in the brain of infants. Lutein made up two-thirds (58%) of carotenoids in the baby's brain. Zeaxanthin accounted for 16% of the carotenoids in the infant's brain

Lycopene was not reported in three infants [45]. A study on the consumption of a carotenoid-containing diet in infants aged 2 to 11 months showed that beta-carotene was the primary carotenoid from the diet. Only 17% of the total carotenoids obtained through food are lutein.  In other words, even though the most carotenoid received through food and the most carotenoid in blood serum is beta-carotene, the most carotenoid in the brain is lutein, which indicates its selective and preferential absorption. The level of lutein and xanthine decreases in MCI, Alzheimer's, and vascular dementia (compared to the healthy control group of the same age).  The level of oxidative substances such as 8-hydroxyl 2' deoxyguanosine (8-OHdG = a registered biomarker for DNA as an oxidative agent) increases in Alzheimer's(46).

In Alzheimer's disease, the phospholipid hydro perohydroperoxides level in red blood cells increases.  Decrease in plasma lutein level is correlated with an increase in 8-OHdG level (ratio: p<0>

- on 1092 older adults without dementia

 Observations: a 10-year follow-up showed the reverse relationship between dementia and Alzheimer's with plasma lutein levels  [48].

A study by Akbaraly et al.

- 589 participants

- Observations: score lower than 25th percentile, in the neurophysiological test ---> low plasma zeaxanthin level less than 25th percentile [49].

A study in Ireland

4453  people aged 50 and over

- Two global tests were MMSE (Mini-Mental State Examination), MoCA (Montreal Cognitive Assessment), and other cognitive tests that evaluated specific cognitive areas.

- Observations: low MPOD ---> low MMSE and MoCA scores and poor performance in prospective memory tests, poor executive function, low mental processing speed, poor sustained attention(50) Average range of MMSE 28.6 to 28.2 and MoCA 25.2 to 24.6 [50].

More MPOD, more processing speed and less reaction time, and better brain-eye communication [51].

Relationship between MPOD and cognitive performance in humans and primates:

• The concentration of lutein in the retinal areas is constantly related to its concentration in the occipital cortex (the primary visual processing area).
• In primates, additional macula-brain relationships were found: lutein, zeaxanthin, and cerebellum - lutein and pons - zeaxanthin and frontal cortex
• Evidence showed that MPOD could be a non-invasive biomarker for lutein and xanthine concentration [52]

Johnson et al.'s study

- Randomized, double-blind, placebo-controlled study

1.lutein ,2. docosahexaenoic, 3. a combination of both (lutein and docosahexaenoic),4. Placebos were given to 49 healthy women aged 60 to 80 years.

• In a way that separates the supplements, improvement in the verbal fluency score (a measure of executive function, which is one of the frontal lobe abilities) was achieved.
•  In the way of combining the supplements, the improvement of the shopping list, word list, and delayed recall memory was achieved
•  It was one of the first studies of its kind that determined the role of lutein in the cognitive function of older people [53].

• The higher the level of lutein, choline, and docosahexaenoic, the stronger the baby's recognition memory
• Lutein is related to fatty acids, phospholipids, antioxidants, and amino acid neurotransmitters in the brain, and with this connection, it causes learning and focused memory.
• - Correlation of lutein with STARD3 (specific binding protein for lutein previously identified in the retina) which shows the selective accumulation of lutein in the brain

Effects of lutein on the heart and cardiac disease

Lutein shows the dominant cardioprotective function and can be used for treating heart disorders related to myocardial infarction [9]. It also prevents angiotensin II-induced cardiac remodeling through suppression of IL-11 expression and reduces heart failure, so consumption of lutein can be a future treatment for cardiac remodeling [54, 55]. Lutein improves glucose intolerance and can be used as a co-adjuvant treatment for heart-related oxidative stress-related diseases caused by hyperglycemia [56]. Lutein can protect the heart from doxorubicin-induced toxicity by preventing oxidative stress [57]. It can be used as an adjuvant and Doxorubicin to decrease its side effects.

No experiment on groups of rats [9] after isoproterenol induction showed that rats pre-treated with 40 mg of Lutein for 4 weeks had decreased infarct size, lipid peroxidation product, and cardiac markers; in this group of rats, antioxidants were increased, and histopathological changes were reversed; therefore, lutein improved cardioprotective activity. In another research, Doxorubicin's side effects were considered, and lutein's effect on ameliorating doxorubicin-induced cardiac toxicity was measured [57]. They started an oral application in rats of lutein for 15 days before administering Doxorubicin. Then 24 hours after doxorubicin application, serum markers were measured to determine toxicity induced by doxorubicin. The result showed that serum markers of cardiac injury in the group that was pretreated with lutein had decreased significantly than in other groups. There's an experiment on two groups of rats with streptozotocin-induced hyperglycemia to investigate lutein's effect on the heart through polyol pathway enzymes and oxidative stress markers. They selected two groups of rats and injected them with streptozotocin which caused hyperglycemia. Then one group received micellar lutein (39 nmol/day/rat), and the other received micelle without lutein for approximately two months. After testing these groups and measuring glucose tolerance, they discovered that lutein causes better glucose tolerance and can prevent cardiac injury in hyperglycemic rats by enhancing different activities in the polyol pathway and oxidative stress markers [58]. In vitro experiments with groups of rats were done [54], and angiotensin II was injected at a dose of 1.4 mg/kg/day for 4 weeks. Consequently, cardiac remodeling occurred, then lutein was injected into one group to determine its effect on cardiac remodeling. The result showed that lutein has a powerful effect on oxidative stress, which can cause cardiac remodeling and heart failure. They indicated that lutein somehow prevents angiotensin II-induced cardiac remodeling and heart attack [59].

Effects of lutein as a carotenoid pigment on skin's function and appearance

As the body's biggest organ, the skin is exposed to many rays like blue-violet, which can cause the degradation of antioxidants and the generation of free radicals [60]. Free radicals and photo-oxidative damage can increase the chance of diseases like Dermatitis, Urticaria, Dermatitis, Skin Cancer &, etc. [61]. Protective mechanisms in the skin:

• First, skin cells are protected by antioxidants. Sunlight can cause the creation of free radicals in skin cells, the effects of which are neutralized by antioxidants.
• Second, cells are called melanocytes in skin with production. The storage of melanin causes the process of tanning and darkening of the skin and can protect the skin by absorbing and filtering the rays of sunlight.
• The third is the hyperplasia of the cells below the epidermis, which causes an increase in thickness, and the sunlight must travel a longer path to reach the lower layers of the skin, effectively reducing skin damage [62].

Among the above three methods, the first method, or the antioxidants present in the skin during exposure to light, provide the only type of immediate protection against damage caused by sunlight. When exposed to sunlight, they can be used to deal with. It will be available immediately. So the other two methods (hyperplasia and melanin) cannot create an immediate protective response. So the importance of antioxidants in the skin is more than the other two [63]. Researchers consider the reduction of antioxidant capacity related to UV rays. Still, studies show that visible wavelengths can also create free radicals in the skin and be effective in this regard; from this conclusion, whether a person is indoors or outdoors, he is constantly exposed to the damage of free radicals. Blue light is almost twice as adequate as the red light in producing free radicals among the visible wavelengths. Therefore, there should be a protective way for this part of the visible wavelength [64]. Even the best sunscreens cannot provide significant protection against visible wavelengths. Even sunscreen products that protect against UVA (longer wavelengths of UVA) (such as micronized titanium dioxide and zinc oxide) have poor absorption at the longest UVA wavelengths or above 370 nm. So we need a substance that can have protective effects against visible blue wavelengths. Like the eyes, lutein in the skin may also have the capacity to absorb blue wavelengths. [65], lutein has protective effects against them, preventing several skin diseases [66]. In addition to its preventive effect, lutein can be used to lighten skin. Skin health and appearance can be improved by lutein supplements[67]. High-dose lutein supplements can increase carotenoid skin levels [68], so it can prevent the occurrence and development of metabolic syndrome [69]. Lutein attenuates inflammatory responses in skin cells and inhibits the expression of pro-inflammatory genes [70]. lutein can improve skin health by increasing gene expression and biosynthesis of hyaluronic acid, which increases cell growth and can be used for treatment [71].

Due to a clinical trial over a 12-week supplementation period which was completed by 46 healthy subjects [67], an oral dietary supplement containing 10 mg lutein (L) and 2 mg zeaxanthin isomers (Zi) or placebo was administered for 12 weeks. The minimal erythemal dose and skin lightening were measured via Chromameter®. As a result, general skin tone and luminance were considerably improved. In another trial, the effect of a high-dose lutein/zeaxanthin supplement on macular pigment optical density (MPOD) and skin carotenoid (SC) levels in 16 Japanese subjects was measured [68]. They were given a supplement containing 20 mg/day of lutein, 4 mg/day of zeaxanthin, and other antioxidants for 16 weeks. As a result, MPOD in week 8 and SC levels in week 4 considerably started to increase and continued to grow until week 16. However, the increase rate of MPOD was significantly higher in subjects with BMI less than 25 kg/m2 compared to other subjects. No serious adverse event was observed in this test. Recent studies indicate that Topical type or oral type of xanthophylls, each separately, can reduce lipid peroxidation, increase skin elasticity, increase skin surface lipid, increase skin hydration simultaneously, and the combined use of oral and topical types increases these effects [72]. In research done by Jueun Oh, Ji Hye Kim, and their colleagues [70], they tried to examine the effect of lutein on the inflammatory responses of skin-derived keratinocytes or macrophages to clarify the mechanism of its inhibitory action. They explored the signaling pathway and factors in cells and discovered that lutein decreases the activation of redox-sensitive AP-1. Therefore, lutein considerably reduced skin inflammatory responses. Their findings also indicate that this effect results from lutein's vigorous antioxidant and p38/JNK inhibitory activities. An in vitro keratinocyte culture was examined to elucidate the effect of xanthophylls lutein and zeaxanthin on skin health through gene expression and biochemical pathways [71]. As a result, they found that 176 genes were noticeably suppressed, whose activity was the expression of peptidase inhibitors. On the other hand, 47 genes were considerably up-regulated, which induced biosynthetic pathways for glycosaminoglycans. All of these effects increased the biosynthesis of hyaluronic acid, which improves skin health.