葉黃素.Lutein

ABOUT LUTEIN:

Lutein is a natural pigment of the carotenoid family. It is widely found in nature, mainly in vegetables and fruits. In the human body, Lutein is found in tissues such as liver, pancreas, ovaries, testicles and in the macula, lens and retina of the eye. Just like other carotenoids, Lutein acts as an antioxidant, protecting cells against the damaging effects of free radicals and/or as a filter in light sensitive tissues such as the eye macula, lens and retina. Unlike ß-Carotene, Lutein is not a Vitamin A precursor.

Lutein and its structural isomer zeaxanthin are compounds that belong to a large class of plant pigments referred to as carotenoids. Of the two, lutein is present in a greater amount in the diet and in human blood and tissues (Johnson et al, 2000, Holden et al, 1999; Sommerberg et al, 1998; Hammond et al, 1997; Hart et al, 1995). Lutein is more polar than many other carotenoids due to the presence of hydroxyl groups on the cyclic ring structure. The relatively higher polarity of lutein compared to other carotenoids determines, in part, distinctive characteristics during absorption, transport, metabolism and uptake into tissues (Erdman et al, 1993; Castenmiller & West 1998; Parker et al, 1999). Unlike the provitamin A carotenoids, (alpha-, beta-carotene and cryptoxanthin), it cannot be converted to vitamin A. Its presence in human blood and tissues (including the macula of the eye) is entirely due to the ingestion of food or supplement sources of lutein, that is, it is not synthesized by human or animal tissue. The two foods that were found to have the highest amount of lutein are kale and spinach (Holden et al, 1999, Mangels et al, 1993). Other major sources include broccoli, peas, and brussel sprouts.

LUTEIN IN NATURE:

Lutein in nature is found mainly in vegetables. In general terms, Lutein is found in the green parts of plants and it is an important component of fruits, petals and some seeds. In the green parts of plants, in fruits and in seeds, Lutein is found in its free form, meaning that it does not have any other types of molecules attached to it. On the other hand, Lutein found in flower petals is chemically bound to various types of fatty acids. In these cases it is said that Lutein is esterified and is commonly known as Lutein Ester.

Free Lutein as found in vegetables, fruits or seeds.

Lutein Ester found in flower petals

LUTEIN AS A NUTRACEUTICAL INGREDIENT:

In the nutraceutical industry there are several suppliers of Lutein, whether free or esterified. Those suppliers offering products with a high concentration of Lutein use marigold flower extracts as raw material. Other suppliers offer dehydrated spinach or alfalfa meal as sources of Lutein. In general these products offer a very low content (<0.5%) of Lutein.

In the nutraceutical market, Lutein is found in different presentations such as tablets, hard gelatin capsules or soft gelatin capsules known as "capsugel". Lutein is commonly blended with other ingredients (vitamins, minerals, plant extracts, etc.), but there are also presentations that contain only Lutein as a sole active ingredient.

FREE LUTEIN versus LUTEIN ESTER:

Free Lutein and Lutein Ester consumed as food and food supplements have similar bioavailability as reported in several scientific studies on humans. These studies have shown that Lutein Ester is equally absorbed as free Lutein by the body. Lutein Ester is hydrolyzed in the digestive tract and converted into free Lutein as it passes through the gut and then it is delivered to the blood flow and to the different tissues where it is deposited such as the eye macula.

In fact some of the studies conducted to determine the effect of lutein supplementation on the eye macula pigment showed that supplementation with Lutein Ester produced an increase in the density of the macular pigment as well as an increase in the concentration of lutein in blood serum.

Lutein and Zeaxanthin:

DESCRIPTION:

Lutein and zeaxanthin are members of the carotenoid family, a family best known for another one of its members, beta-carotene (see Beta-Carotene). They are natural fat-soluble yellowish pigments found in some plants, algae and photosynthetic bacteria. They serve as accessory light-gathering pigments and to protect these organisms against the toxic effects of ultra-violet radiation and oxygen. They also appear to protect humans against phototoxic damage. Lutein and zeaxanthin are found in the macula of the human retina, as well as the human crystalline lens. They are thought to play a role in protection against age-related macular degeneration (ARMD) and age-related cataract formation. They may also be protective against some forms of cancer. These two carotenoids are sometimes referred to as macular yellow, retinal carotenoids or macular pigment.

Food sources of lutein and zeaxanthin, include corn, egg yolks and green vegetables and fruits, such as broccoli, green beans, green peas, brussel sprouts, cabbage, kale, collard greens, spinach, lettuce, kiwi and honeydew. Lutein and zeaxanthin are also found in nettles, algae and the petals of many yellow flowers. In green vegetables, fruits and egg yolk, lutein and zeaxanthin exist in non-esterified forms. They also occur in plants in the form of mono-or diesters of fatty acids. For example, lutein and zeaxanthin dipalmitates, dimyristates and monomyristates are found in the petals of the marigold flower (Tagetes erecta). Many of the marketed lutein nutritional supplements contain lutein esters, with much smaller amounts of zeaxanthin esters, which are derived from the dried petals of marigold flowers.

Lutein dipalmitate is found in the plant Helenium autumnale L. Compositae. It is also known as helenien and it is used in France for the treatment of visual disorders. Zeaxanthin in its fatty acid ester forms, is the principal carotenoid found in the plant Lycium chinese Mill. Lycium chinese Mill, also known as Chinese boxthorn, is used in traditional Chinese medicine for the treatment of a number of disorders, including visual problems.

Lutein and zeaxanthin belong to the xanthophyll class of carotenoids, also known as oxycarotenoids. The xanthophylls, which in addition to lutein and zeaxanthin, include alpha-and beta-cryptoxanthin, contain hydroxyl groups. This makes them more polar than carotenoids, such as beta-carotene and lycopene, which do not contain oxygen. Although lutein and zeaxanthin have identical chemical formulas and are isomers, they are not stereoisomers, as is sometimes believed. They are both polyisoprenoids containing 40 carbon atoms and cyclic structures at each end of their conjugated chains. Also, they both occur naturally as all-trans (all-E) geometric isomers. The principal difference between them is in the location of a double bond in one of the end rings. This difference gives lutein three chiral centers rather than the two that are found in zeaxanthin. The chemical structures are illustrated below.

Lutein

Owing to its three chiral centers, there are 23 or 8 stereoisomers of lutein. The principal natural stereoisomer of lutein is (3R,3'R,6'R)-lutein. Lutein is also known as xanthophyll (also, the group name of the oxygen-containing carotenoids), vegetable lutein, vegetable luteol and beta, epsilon-carotene-3,3'diol. The molecular formula of lutein is C40H56O2 and its molecular weight is 568.88 daltons. The chemical name of the principal natural stereoisomer of lutein is (3R,3'R,6'R)-beta,epsilon-carotene-3,3'-diol.

ACTIONS AND PHARMACOLOGY-

ACTIONS:

Lutein and zeaxanthin may be ophthalmoprotective.

MECHANISM OF ACTION:

Lutein and zeaxanthin, which are naturally present in the macula of the human retina, filter out potentially phototoxic blue light and near-ultraviolet radiation from the macula. The protective effect is due in part, to the reactive oxygen species quenching ability of these carotenoids. Further, lutein and zeaxanthin are more stable to decomposition by pro-oxidants than are other carotenoids such as beta-carotene and lycopene. Zeaxanthin is the predominant pigment in the fovea, the region at the center of the macula. The quantity of zeaxanthin gradually decreases and the quantity of lutein increases in the region surrounding the fovea, and lutein is the predominant pigment at the outermost periphery of the macula. Zeaxanthin, which is fully conjugated (lutein is not), may offer somewhat better protection than lutein against phototoxic damage caused by blue and near-ultraviolet light radiation.

Lutein and Zeaxanthin, which are the only two carotenoids that have been identified in the human lens, may be protective against age-related increases in lens density and cataract formation. Again, the possible protection afforded by these carotenoids may be accounted for, in part, by their reactive oxygen species scavenging abilities.

PHARMACOKINETICS:

Lutein and zeaxanthin exist in several forms. Nutritional supplement forms are comprised of these carotenoids either in their free (non-esterified) forms or in the form of fatty acid esters. Lutein and zeaxanthin exist in a matrix in foods. In the case of the chicken egg yolk, the matrix is comprised of lipids (cholesterol, phospholipid, triglycerides). The carotenoids are dispersed in the matrix along with fat-soluble nutrients, including vitamins A, D and E. In the case of plants, lutein and zeaxanthin are associated with chloroplasts or chromoplasts.

The efficiency of absorption of lutein and zeaxanthin is variable, but overall appears to be greater than that of beta-carotene. Esterified forms of these carotenoids may be more efficiently absorbed when administered with high-fat meals (about 36 grams), than with low-fat meals (about 3 grams). Lutein and zeaxanthin esters are hydrolyzed in the small intestine via esterases and lipases. Lutein and zeaxanthin that are derived from supplements or released from the matrices of foods, are either solubilized in the lipid core of micelles (formed from bile salts and dietary lipids) in the lumen of the small intestine, or form clathrate complexes with conjugated bile salts. Micelles and possibly clathrate complexes deliver lutein and zeaxanthin to the enterocytes.

Lutein and zeaxanthin are released from the enterocytes into the lymphatics in the form of chylomicrons. They are transported by the lymphatics to the general circulation via the thoracic duct. In the circulation, lipoprotein lipase hydrolyzes much of the triglycerides in the chylomicrons, resulting in the formation of chylomicron remnants. Chylomicron remnants retain apolipoproteins E and B48 on their surfaces and are mainly taken up by the hepatocytes and to a smaller degree by other tissues. Within hepatocytes, lutein and zeaxanthin are incorporated into lipoproteins. Lutein and zeaxanthin appear to be released into the blood mainly in the form of high-density lipoproteins (HDL) and, to a lesser extent, in the form of very-low density lipoprotein (VLDL). Lutein and zeaxanthin are transported in the plasma predominantly in the form of HDL.

Lutein and zeaxanthin are mainly accumulated in the macula of the retina, where they bind to the retinal protein tuberlin. Zeaxanthin is specifically concentrated in the macula, especially in the fovea. Lutein is distributed throughout the retina.

The form of lutein in the plasma is (3R,3'R,6'R)-lutein. Zeaxanthin found in plasma is predominantly (3R,3'R)-zeaxanthin. Lutein appears to undergo some metabolism in the retina to meso-zeaxanthin.

Lutein (LOO-teen) is one of over 600 known naturally occurring carotenoids. Found in green leafy vegetables such as spinach and kale, lutein is employed by organisms as an antioxidant and for blue light absorption. Lutein covalently bound to one or more fatty acids is present in some fruits and flowers, notably marigolds (Tagetes). Saponification of lutein esters yields lutein in approximately a 2:1 weight-to-weight conversion.

Lutein is a lipophilic molecule and generally insoluble in water. The presence of the long chromophore of conjugated double bonds (polyene chain) provides the distinctive light-absorbing properties. The polyene chain is susceptible to oxidative degradation by light or heat and is chemically unstable in acids.

The principal natural stereoisomer of lutein is (3R,3'R,6'R)-beta,epsilon-Carotene-3,3'-diol.

PROPERTIES:

CHEMICAL-Organic, carotenoid, biological anti-oxidant,

PHYSICAL (in purified form)-yellow colored slightly hydroscopic crystalline solid

FORMULA C40 H52 O2

MOLECULAR WEIGHT 644

General
Synonyms	Luteine; Lutein ester; trans-lutein; beta,epsilon-Carotene-3,3'-diol
IUPAC Name	4-[18-(4-hydroxy-2,6,6-trimethyl-1-cyclohexenyl) -3,7,12,16-tetramethyl-octadeca -1,3,5,7,9,11,13,15,17-nonaenyl] -3,5,5-trimethyl-cyclohex-2-en-1-ol
CAS Number	127-40-2
Chemical formula	C40H56O2
Chemical properties
Molecular weight	568.871 g/mol
Color	Red-orange
Form	Crystalline
Solubility	Organic/fat soluble, aqueous insoluble
λmax	446 nm
Toxicity	GRAS
Deficiency symptoms
Eye damage Pale, dry skin
Excess symptoms
Carotenodermia
Common sources
Leafy vegetables Egg yolk Darkly colored fruits Marigold petals

Lutein Molecule

Figure 1. Inverse relation between change in carotid IMT and quintiles of plasma lutein. Graph depicts IMT means within lutein quintiles (median) for women (; n=214) and men (; n=248) adjusted for cardiovascular risk factors (see Methods). Ranges of plasma lutein concentrations (µmol/L) for consecutive quintiles were 0.070 to 0.182, 0.184 to 0.240, 0.244 to 0.296, 0.297 to 0.360, and 0.367 to 0.805 for women and 0.019 to 0.180, 0.184 to 0.230, 0.231 to 0.279, 0.280 to 0.347, and 0.350 to 0.790 for men. Error bars indicate SEM. From the Los Angeles Atherosclerosis Study.

No statistically significant interactions were detected between sex, ethnicity, smoking status, use of antihypertensive medication, or use of cardiovascular medications and the relation of plasma lutein to progression of IMT. The inverse relation was statistically significant among nonsmokers (P=0.03) and smokers (P=0.005).

In contrast, the association between progression of IMT and plasma ß-carotene was not significant (P for trend=0.15, multivariate model), and the point estimate was attenuated by inclusion of plasma lutein as a covariate (P for trend=0.22).

LDL Oxidation by Artery Wall Cells:

Lutein was highly effective in a dose-dependent manner in reducing the attraction of monocytes in the coculture model of lipoprotein oxidation in the artery wall. Figure 2 depicts the results for the 2 types of chemotaxis assays. A dose-dependent reduction in chemotaxis for monocytes is apparent for increasing concentrations of lutein in each of the experiments. A dramatic inhibitory effect of lutein on chemotaxis occurs with pretreatment of the coculture cells. Note that lutein at 100 nmol/L inhibits monocyte migration at a level similar to that observed for human HDL. The measured concentrations of lutein in plasma from the human cohort ranged from 20 to 930 nmol/L.

Figure 2. Effect of pretreatment with lutein on LDL oxidation and resulting monocyte chemotactic activity. A, LDL was incubated with lutein. Values are mean±SD for quadruple cocultures. B, Cocultures were preincubated with lutein. *P<0.05.

Figure 3. Aortic lesion size in ascending segment of aortic arch among apoE-null mice. Measurements were missing from 4 animals (3 chow, 1 lutein). Lesion size was reduced in lutein condition by 44% (P=0.009).

Lutein supplementation reduced the level of lipid hydroperoxides [13(s)HPODE] in plasma from apoE-null mice by 30% (P<0.05). Hemoglobin release (OD 540) due to in vitro red cell fragility was also significantly reduced (P<0.05) in the lutein condition. In addition, there was a significant 33% reduction in the levels of plasma VLDL+IDL in the group supplemented with lutein compared with the chow-fed mice (P<0.001). No significant changes were observed in plasma LDL or HDL levels.

Lutein supplementation resulted in a marked reduction in the lipid hydroperoxide formation when LDL from the 2 groups was incubated in cocultures (Figure 4A). In addition, monocyte chemotactic activity induced by LDL oxidation was markedly reduced when LDL from mice supplemented with lutein was incubated in the artery wall cocultures (Figure 4B).

Figure 4. Effect of dietary supplementation with lutein on LDL oxidation by artery wall cocultures. Plasma was obtained from blood of apoE-null mice maintained on chow or chow supplemented with lutein (+Lutein). Samples consisted of those from 20 mice at week 0 (Chow, 0 week) or from 10 mice maintained on chow for 8 weeks (Chow, 8 week) or 10 mice fed lutein-supplemented chow for 8 weeks (+Lutein, 8 week). Monocyte chemotactic activity was determined (B) as described in Methods. Control values for background (No Addition), human LDL control (h LDL), and human LDL+human HDL control (h LDL+h HDL) are included. Values are mean±SD of quadruple samples assayed. *P<0.05.

Connection with Plants:

In this era of biochemistry, we're rediscovering our vital connection with plant life. Although research into phytonutrients is relatively new, many plant compounds are being found in significant concentrations in the human body. Their presence in our blood serum, organs, and mothers' milk suggests they play an important role in our body chemistry, and perhaps explains why we've appreciated them as foods throughout history. Like many carotenoids, lutein has evolved as an integral part of human biochemistry, with lutein providing many benefits to our well-being. Since mammals cannot synthesize it, lutein must be obtained from the diet.Lutein is extracted from specially grown marigold flowers high in Lutein, and then purified.

Carotenoids:

Later researches confirmed that carotenes and xanthophylls are close related in molecular structure, and Harold Strain coined the word “carotenoids” to refer to the entire group of diverse, and yet closely related substances. Major known functions of these phytochemicals are photoreception and photo protection. Zeaxanthin and antheraxanthin, other members in the family, are also found to be involved in heat (energy) dissipation by converting themselves to violaxanthin, thus adding additional measures for the protection of photosynthesis systems.

Anti-Oxidant:

In addition to being an integral part of photosynthesis systems as photoreceptors and protectors, carotenoids are strong anti-oxidants and protects plant tissues from damages caused by free radicals formed by UV-irradiation, etc. When we eat carotenoids such as beta-carotene, lutein, and pycopene through food, they protect our body against oxidative and free radical damages as well.

In addition to anti-oxidant actions, beta-carotene converts in our body to Vitamin A, which is an essential for our body functions including vision. Like beta-carotene, lutein is a carotenoid found commonly in diets. Studies indicate lutein is an essential nutrition for healthy eyes and vision.

Protect Cells:

Lutein and zeaxanthin are carotenoids found in many fruits and vegetables, and are stored in the macula of the eyes, where they protect against free radical damage and reduce the risk of macular degeneration. One in vitro study suggested that lutein and zeaxanthin protected the membranes from free radical damage. They may also protect against free radical damage induced by ultraviolet light.

In general, individuals who consume large quantities of the vegetables and fruits that contain lutein may be less likely to develop cataracts and age-related macular degeneration (AMD) than individuals with a lutein-poor diet. AMD results from the deterioration of the retina's central section. Partial or total vision loss may occur. Lutein is one of the two most common pigments (coloring agents) in the retina. It is believed to block out blue light and to protect retinal tissue from being damaged by light. In older individuals, the layer of yellow pigment in the retina tends to become thinner, increasing the chance for AMD. Taking lutein may thicken the yellow layer. In addition, lutein acts as an antioxidant to protect the interior of the eyes from damage by oxygen free radicals, natural chemicals produced in the body. Although a recent very large observational study of humans failed to prove that lutein affected the development of glaucoma, some earlier evidence suggests that lutein may help prevent some types of glaucoma, as well. Further studies are being conducted to better understand lutein's possible role in glaucoma.

Consumption of vegetables and fruits has long been associated with reduced rates of heart disease and some cancers. Because lutein is a major component of some plant foods known to be among the most protective, its antioxidant effects are thought to play a major part in preventing these conditions. In animal and human studies, lutein has been investigated for possible effects against atherosclerosis (hardening of the arteries). However, results from several human studies conflict with each other. While some seem to show that high lutein levels correlate with lower risk of atherosclerosis, other studies find little or no anti-atherosclerotic effect from lutein. While generally positive, results from studies of lutein in cancer are mixed, too. For cancer prevention, lutein is believed to increase the death rate of cancer cells. At the same time, it may decrease the growth of blood vessels that supply cancerous tumors. In laboratory studies, lutein has also appeared to change the ways that DNA repairs itself. Lutein has shown some effectiveness in studies of breast, colon, lung, and ovarian cancers in humans. Additionally, in laboratory mice, oral doses of lutein reduced the extent of skin damage from exposure to ultraviolet light. A possible protective effect from skin cancer may result. However, in an observational study of over 1,000 individuals in China, high blood levels of lutein seemed to be related to a slightly increased risk of having stomach cancer. The use of lutein in both heart disease and cancer needs more study.

Lutein (LOO-teen) is a nutrient found in vegetables and fruits. Lutein naturally filters damaging, high-energy blue light from the visible light spectrum. When blue light makes contact with the eyes and skin, it may induce harmful oxidative stress within skin and retinal cells. Lutein may protect cells by absorbing blue light. This makes lutein unique from other antioxidants such as vitamin C or beta-carotene. Lutein also acts as an antioxidant, protecting cells against the damaging effects of free radicals.

Lutein is found naturally in the body, but Lutein is not made in the body.

Lutein must be obtained from food or dietary supplements.

Lutein is the only purified lutein identical to that found in nature. Like the lutein in green vegetables, Lutein is biologically active and can be readily absorbed by the body. Lutein can be found in many leading nutritional supplements, as well as fortified foods and skin care products.

Lutein is a carotenoid found in vegetables and fruits. It is not made in the body and can only be obtained through large amounts of certain fruits and vegetables or through food and vitamin supplements. Products containing lutein are in high demand by consumers who don't have time or don't choose to consume enough lutein in their diets.

Lutein is the primary carotenoid found in the macula, which is the central part of the retina. Lutein has been found in the eye, serum, skin, cervix, brain and breast. Within the human eye, lutein deposits itself in the macular region as well as the entire retina, ciliary iris bodies and lens. While not a vitamin, lutein is an antioxidant that may help protect the macula tissue from destructive oxidation reactions by quenching free radicals. Lutein also filters high-energy blue light that can damage the macula and skin.

Researchers at Harvard found that eating 6 mg of lutein a day lowered the odds of macular degeneration, a leading cause of blindness in older people, by 43%. According to several studies, loading up on lutein also seems to reduce the odds of cataracts by 20% to 50%.

Lutein is found abundantly in green leafy vegetables such as spinach and kale, but few people eat enough to get an adequate intake of lutein. In order to consume the recommended 6 mg per day, one must eat a large bowl of spinach salad or equivalent.

Vitabase used lutein extract in Lutein Plus, because it is the highest quality lutein on the market. Lutein is purified from marigold extract using patented processes so consumers can be sure supplements containing Lutein contain the same lutein that is found in nature.

Unlike lutein esters, lutein is chemically identical to lutein found in spinach, kale, collard greens, and other green leafy vegetables in our diet. In fact, 93 percent of the lutein absorbed by the human body is present as lutein - not lutein esters.

Carotenes and xanthophylls, the brilliant yellow pigments, were isolated in 1831 from carrot root by Heinrich Wilhelm Ferdinand Wackenroder (1789-1854), and from yellow autumn leaves in 1837 by Berzelius, respectively. In Greek, "xantho" means yellow, and "phylls" stands for leaves, which is comparable to "chlorophylls" (green leaves). Many scientific studies ensued, and by 1902, there were over 800 publications in the field of carotene research. Xanthophylls were found in algae, and lutein, a component of xanthophylls was found in egg yolks. Later researches confirmed that carotenes and xanthophylls are close related in molecular structure, and Harold Strain coined the word "carotenoids " to refer to the entire group of diverse, and yet closely related substances. Major known functions of these phytochemicals are photoreception and photoprotection. Zeaxanthin and antheraxanthin, other members in the family, are also found to be involved in heat (energy) dissipation by converting themselves to violaxanthin, thus adding additional measures for the protection of photosynthsis systems.

Lutein intakes at levels achievable through diet are considered to be safe. There are no known reports that lutein, at any level of intake has toxic effects. With the advancement of the supplement industries, it is now possible to consume levels of lutein that are beyond typical dietary intakes. However, the results of several human intervention studies that indicate that supplementation of pharmacological doses of b-carotene (another common dietary carotenoid0, did not decrease the risk of cancer or cardiovascular disease, and might even be harmful to smokers or former asbestos workers (ATBC, 1994; Omenn et al, 1996). It is not know if there are similar risks associated with high supplemental intakes of lutein. Certainly, supplementation with high doses of lutein raises its blood levels (Table 1). For example, in a group of apparently healthy non-smokers supplemented with lutein (15 mg/day for 4 months) resulted in the presence of ester forms of lutein was found in the serum in those subjects reaching serum levels above 1.05 umol/L (Granado et al 1998) (compared this to 0.37 umol/L median value and 0.69 fir 90th percentile for the Third NHANES survey, (Ford & Giles, 2000)). The physiological significance of this in not known, particularly since the esters forms amounted to approximately 3% of the total lutein value. This observation is specific to lutein supplementation, that is, it has not been observed of other major dietary carotenoids, such as b-carotene and lycopene at supplementation at similar doses (Johnson et al, 1996, 1997a, 1997b).

Summary:

The biological actions attributed to lutein (including its selective accumulation in the retina), along with the clinical and epidemiological evidence in relation to age-related macular degeneration, as prompted interesting in the role of lutein in the prevention of this major cause of blindness.

Although the epidemiology has not been entirely consistent in showing a protective association between lutein and risk of AMD, there have been no studies (case-control, clinical, epidemiologic, animal) that have shown lutein to be associated with an increased risk of AMD, or any other disease. There evidence suggests that lutein can prevent or delay the progression AMD. However, there is no evidence that suggests that lutein can cure AMD.