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Astaxanthin and eye health: the newest carotenoid dietary supplement solution.

There's a very good chance that, in the last 24 hours, you've eaten several different carotenoids. This class of naturally occurring isoprenoid-based antioxidant molecules includes more than 600 unique compounds; however, most people are only familiar with a few of the most important carotenoids. These include lycopene, the colour of red tomatoes, zeaxanthin, the colour of yellow corn, and beta-carotene, the colour of orange carrots. In addition, Vitamin A, or retinol, is an essential vitamin for human eye health, which is available in many vegetables and can also be manufactured in vivo from dietary beta-carotene on an as needed basis. The vitamin in its oxidized form, as retinal, serves as a key component in the functioning retina. Chronic Vitamin A deficiency leads to total blindness in humans.

Carotenoids are divided into two distinct structural groups; namely, carotenes that contain no oxygen atoms (typical examples are lycopene and beta-carotene) and the xanthophylls whose noteworthy examples include lutein and zeaxanthin. Xanthophylls are all characterized by the fact that they contain oxygen atoms added to the structures of the simpler carotenes. Interestingly, none of the carotenes tested to date, and few of the xanthophylls tested to date, pass through the blood-brain-barrier--with a few notable exceptions. These exceptions include lutein, zeaxanthin, canthaxanthin and astaxanthin.

Human serum typically contains about ten carotenoids. The major carotenoids in human serum include beta-carotene, alphacarotene, cryptoxanthin, lycopene and lutein. Small amounts of zeaxanthin, phytofluene and phytoene are also found in human organs. However, of all of these carotenoids, only zeaxanthin and lutein are found in the human retina. Indeed, the retina has the highest concentration of polyunsaturated fatty acids of any tissue in the human body. It has been theorized that zeaxanthin and lutein are concentrated in the retina because of their ability to quench singlet oxygen and to scavenge free radicals--because they pass through the blood and eye brain barriers and are required in the oxygen-rich environment of the retina to prevent light-mediated free radical damage to the retina. In fact, zeaxanthin is the predominant carotenoid found in the central portion of the retina and, more specifically, is concentrated in the retinal cones located in the central area of the retina (the macula). Lutein, by contrast, is located in the peripheral area of the retina in the rod cells. Therefore, the eye preferentially accumulates zeaxanthin compared with lutein in the critical central macular retinal area (zeaxanthin, interestingly, is a much more effective singlet oxygen scavenger than lutein), where the greatest level of light impinges.

Structure and Function

Biochemists have determined the exact, yet complicated, mechanism for the light sensory response in the eye. It involves a key protein called rhodopsin whose structure includes a bound polyunsaturated compound called retinal (retinal is structurally related to vitamin A). When light enters the eye, cisretinal isomerizes to all its all-trans isomer, causing disassociation of itself from its protein carrier. The disassociation triggers a complicated cascade leading to nerve-based transmission of electrons to the brain via the optic nerve. All of this "photochemistry" takes a mere 200 femtoseconds to occur, making it one of the fastest biochemical-to-electron transformations known.

Chemists have learned that retinal is highly susceptible to polymerization by localized free radicals and highly reactive singlet oxygen. Because retinal is a strong absorber of light and because the retina is highly vascularized, and thus rich in dissolved oxygen, nature has provided zeaxanthin as the key retinal carotenoid for protection of the retina from light-induced damage at that point in the centre of the retina where the most significant light impingement occurs. Clinical studies in humans indicate that photic injury is a cause of age-related macular degeneration because of the cumulative effect of repeated photic insult leading to the gradual loss of photoreceptor cells.

Other naturally occurring antioxidants such as ascorbate have been clearly shown to reduce the loss of rhodopsin in animal experiments after exposure to light, thereby suggesting that ascorbate (vitamin C) can protect against retinal injury owing to excessive light energy. Indeed, high levels of ascorbate are found in retinal tissue in humans. Therefore, antioxidants that can cross the blood-brain/eye barrier would be expected to provide enhanced protection of the retina, particularly if the antioxidant can reach the central retinal macula.

Xanthophylls Are Go!

One naturally occurring xanthphyll that is able to cross the blood-brain/eye barrier is canthaxanthin; however, scientists have observed that chronic ingestion of canthaxanthin at high doses for extended periods of time leads to the deposition of canthoxanthin crystals in the inner layers of the retina. Therefore, the blood retinal pigment epithelium layer permits only particular carotenoids to enter the retina. Thus, only zeaxanthin, lutein and Nature's most potent carotenoid, astaxanthin, appear to have favorable transport properties while lacking side-effects and offering significant antioxidant protection. There have been many clinical trials designed to support the supplementation of the diet with lutein; however, as of 2007, there appears to be no unequivocal evidence that lutein supplementation is necessary in eye healthcare despite its wide acceptance as a supplement (the current retail market for lutein eye healthcare supplements is approximately $160 million). This may simply imply that supplementation with extra lutein is not necessary because it is a readily available xanthophyll in many vegetables. More recently, zeaxanthin has entered the marketplace as an eye healthcare supplement. However, there is an even more potent carotenoid that meets all the requirements associated with eye/blood/ brain barrier transport, accumulation in the macula and is capable of long-term use.


Dr Mark Tso, at the University of Illinois, has clearly demonstrated that astaxanthin is one such naturally occurring antioxidant that meets all of these critical criteria. Astaxanthin is the carotenoid xanthophyll responsible for the red colour in salmon, lobster, krill, crab, other shellfish and in the microalgae Haematococcus pluvialis. The latter source has made astaxanthin readily available worldwide for such use. His work with astaxanthin resulted in the issuance of a US patent (and global equivalents) covering the use of astaxanthin in the prevention of macular degeneration, photic injury, ischemic diseases and inflammatory diseases of the eye and central nervous system. In addition, astaxanthin turns out to be a much more powerful antioxidant than canthoaxanthin, beta-carotene, zeaxanthin, lutein and alpha-tocopherol. Shimidzu, et al., discovered that astaxanthin is 550 times more potent than alpha-tocopherol, 27.5 times more potent than lutein and 11 times more potent that beta-carotene in quenching singlet oxygen. In addition, Bagchi discovered that natural astaxanthin is 14 times more potent than alpha-tocopherol, 54 times more potent that beta-carotene and 65 times more potent that ascorbic acid (vitamin C) in scavenging oxygen free radicals. Thus, in light of the dramatic differences in the potency of astaxanthin when comparing the quenching of singlet oxygen and the scavenging of oxygen free radicals, it is clear that astaxanthin compares very favorably with zeaxanthin and lutein, the two carotenoids that are found naturally in the retina.

One more aspect of carotenoids worth mentioning at this point is that some of them can act as pro-oxidants. This is important, as a carotenoid with pro-oxidant capability actually causes oxidation to occur in the body when high concentrations are present in tissue. Martin, et al., showed that beta-carotene, lycopene and zeaxanthin can become prooxidants under certain conditions; however, because astaxanthin is the most potent of all carotenoids, Beutner, et al., showed that astaxanthin can never--nor has it ever--exhibit any pro-oxidant activity, unlike the zeaxanthin found in the human eye. This would seem to rule out over-supplementation with zeaxanthin in eye helthcare.

In Summary

As humans already have an abundant source of lutein and zeaxanthin in their diets from many vegetable sources and these carotenoids are already present in the human eye, it appears that astaxanthin with its unique properties, unlike lutein or zeaxanthin, is the eye healthcare supplement of choice. Only naturally occurring astaxanthin can provide a new and much more powerful layer of antioxidant protection because, unlike lutein and zeaxanthin, it is not currently present in most human diets (unless you eat at least 8 oz of salmon daily). With astaxanthin's extraordinarily potent antioxidant properties, its ability to cross the blood-brain/eye barrier and concentrate in the retinal macula, without the side-effects seen with canthaxanthin, and in light of Tso's contributions, astaxanthin, in a convenient dietary supplement presentation, is now emerging as the pre-eminent choice for use to supplement the lutein and zeaxanthin already found naturally in our diets. Astaxanthin should be the first choice of eye healthcare supplementation for the management of eye-related oxidative stress and thus the prevention and mitigation of degenerative diseases of the eye, such as macular degeneration.


In addition, Tso found that light-induced damage, photoreceptor cell damage, ganglion cell damage and damage to neurons of the inner retinal layers can be prevented or ameliorated by the use of astaxanthin--including neuronal damage from ischemic, photic, inflammatory and degenerative insult. Tso's patent claims the use of astaxanthin across a wide range of eye diseases including age-related macular degeneration, diabetic neuropathy, cystoid macular edema, central retinal arterial and venous occlusion, glaucoma and inflammatory eye diseases such as retinitis, uveitis, iritis, keratitis and scleritis, all disease states common to eye insult by oxidative species such as free radicals.

For further information

Dr John Minatelli

Senior VP Business Development

Valensa International

2751 Nutra Lane

Eustis, Florida 32726, USA.

Tel. +1 352 357 2004


1. N. Shimidzu, et al., "Carotenoids as Singlet Oxygen Quenchers in Marine Organisms," Fisheries Science 62(1), 134-137 (1996).

2. D. Bagchi, Oxygen Free Radical Scavenging Abilities of Vitamins C, E, [beta]-Carotene, Pycnogenol, Grape Seed Proanthocyanidin Extract, Astaxanthin and BioAstin In Vitro (Creighton University School of Health Sciences, Omaha, Nebraska, USA [2001]).

3. H.D. Martin, et al., "Chemistry of Carotenoid Oxidation and Free Radical Reactions," Pure Appl. 71(12), 2253-2262 (1999).

4. S. Beutner, et al., "Quantitative Assessment of Antioxidant Properties of Natural Colorants and Phytochemicals: Carotenoids, Flavonoids, Phenols and Indigoids. The Role of [beta]-Carotene in Antioxidant Functions," J. Sci. Food Agric. 81, 559-568 (2001).

Further Reading

* T. Hiramitsu, et al., Opthalmic Res. 23, 196-203 (1991).

* K. Kirschfeld, Proc. R. Soc. Lond. B216, 71-85 (1982).

* N.I. Krinsky, et al., J. Natl. Cancer Inst. 69(1), 205-210 (1982).

* M. Kurashige, et al., Physiol. Chem. Phys. & Med. NMR, 22, 22-38 (1990).

* Y. Nagaki, et al., J. Trad. Med. 19(5) 170-173 (2002).

* Y. Nagaki, et al., J. Clin. Therap. Med. 22(1), 41-54 (2006).

* A. Nakamura, et al., Jpn J. Clin. Ophthalmol. 58(6) 1051-1054 (2004).

* T. Nitta, et al., Clin. Med. 21(5), 543-556 (2005).

* J.S. Park, et al., WO 2005/011712 A1 and references therein.

* K. Shiratori, et al., Clin. Med. 21(6) 637-650 (2005).

* Y. Suzuki, et al., Exp. Eye Res. 82(2) 275-281 (2006).

* K. Takahashi, J. Clin. Thera. Med. 21(4), 431-436 (2005).

* M. Tso, et al., US Patent 5,527,533.

* M. Tso, Ophthalmol. 92(5), 628-635 (1985).

RELATED ARTICLE: Keeping an eye on lutein.

Marigold flowers (Tagetes erecta) contain lutein in its ester form, and it is from this natural raw material that all commercially available lutein ingredients are produced. Some are supplied as lutein esters, while others undergo additional manufacturing steps to provide the 'free' unesterified form. Here are five key facts about lutein esters, supported by reputable scientific research.

Lutein Esters Work

Studies investigating both healthy individuals and those with early stage Age-related Macular Degeneration (AMD) show that macular pigment density increases significantly when lutein esters are ingested. Even those with established AMD may benefit from lutein ester supplementation as research results prove that a diseased macula is able to accumulate and stabilize lutein from lutein esters.

Esterification Does Not Impair Bioavailability

The scientific community recognizes lutein esters as a source of lutein because studies consistently show that lutein from lutein esters have excellent bioavailability. In fact, lutein from lutein esters and 'free' lutein are both well absorbed. (1,2)

The Human Body is Naturally Equipped to Release Lutein from Lutein Esters Converting lutein esters into free lutein is not 'hard work' for the human body. It digests and absorbs fat-soluble dietary compounds--such as vitamins A and E and lutein esters--as part of normal, multistage digestion. Lutein esters are naturally and efficiently broken apart releasing lutein, which is then absorbed into the bloodstream. This 'cleaving' stage in the process does not make absorption less effective. Indeed, recent laboratory research predicts that when lutein is ingested in the free form it is more prone to degradation in the stomach. This is likely to reduce the amount reaching the intestine for absorption into the bloodstream. (3)


Lutein from Lutein Esters is Easily Absorbed with Average Fat Intakes Lutein from lutein esters is perfectly well absorbed with an average dietary fat intake. There is no body of evidence to support the claim that they require a high level of dietary fat for adequate absorption. Carotenoids, including lutein, are digested and absorbed in the same way as all fat-soluble dietary compounds and it is therefore necessary to consume them--in both free and esterified forms--with some fat.

Potential Health Benefits Apply to Both Lutein Esters and Free Lutein Any published research on the potential health benefits of lutein in general is as relevant to lutein esters as it is to free lutein, as lutein esters are a recognized source of lutein. Indeed, the scientific community commonly uses the term 'lutein' in research papers irrespective of whether the source is lutein esters or 'free' lutein.


(1.) P.E. Bowen, et. al., "Esterification Does Not Impair Lutein Bioavailability in Humans," J. Nutr. 132, 3668-3673 (2002).

(2) H. Chung, et. al., "Lutein Bioavailability is Higher from Lutein-Enriched Eggs than from Supplements and Spinach in Men," J. Nutr. 134, 1887-1893 (2004).

(3) P. Molnar, et. al., "In Vitro Degradation of lutein but Not Lutein Ester by Gastric pH," Carotenoid Science 10, 1-5 (2006).

About Xangold Natural Lutein Esters from Cognis Nutrition & Health

Xangold is a natural lutein ester concentrate, extracted from marigolds grown exclusively for Cognis to ensure strict control from crop to finished product. Both the product concentrate and the extraction process are patent protected. Xangold undergoes the minimum processing necessary to produce an excellent quality, competitively-priced, natural-source product. It has first-rate stability and is available in multiple forms and concentrations. For more information please call +49 2173 4995 226, e-mail nutrition-and-health-europe@cognis. com or visit
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Title Annotation:eye health
Author:Minatelli, John
Publication:Nutraceutical Business & Technology
Article Type:Cover story
Geographic Code:1USA
Date:Jan 1, 2008
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