OA21150A - Food supplement for eye health. - Google Patents

Abstract

The present invention relates to a food supplement for eye health, a concentrate of nutrients which is in the form of a tablet or capsule composed of Lutein, Zeaxanthin, Astaxanthin, Vitamin C, Vitamin E, Zinc in the form zinc oxide, copper in the form of copper oxide and possibly excipients such as silica dioxide and magnesium stearate. This dietary supplement may prevent and aid in the treatment of age-related macular degeneration (AMD), cataracts, diabetic retinopathy, glaucoma, and various other retinal diseases. Very effective for eye health, this food supplement can be consumed every day for more than 5 years without danger and without notable side effects.

Description

DESCRIPTION OF THE INVENTION

The present invention relates to a dietary supplement for eye health.

No one wants to go blind. Blindness is one of the most feared consequences of various visual impairments. It is essential to combine all possible efforts to avoid avoidable blindness and visual impairment.

It is known that “globally, at least 2.2 billion people have a visual impairment affecting near or distance vision. For at least 1 billion of these people, or almost half of them, visual impairment could have been avoided or has not yet been treated.

• The two leading causes of visual impairment and blindness are uncorrected refractive errors and cataracts.

• The majority of people with visual impairment and blindness are over 50 years old; However, vision loss can affect people of all ages.

• Visual impairment represents an immense financial burden on a global scale: each year worldwide, productivity losses associated with visual impairment attributable to uncorrected myopia or presbyopia are estimated at 244 billion United States dollars (USD) and 25.4 billion USD, respectively. »'

It is also known that a group of 244 Experts from the GBD 2019 (Vision Loss Expert Group of the Global Burden of Disease Study) published a scientific article which attests that 1 billion people whose visual impairment could have been avoided "includes the people with moderate or severe impairment or blindness due to untreated refractive error (88.4 million), cataracts (94 million), glaucoma (7.7 million), eye opacities cornea (4.2 million), diabetic retinopathy (3.9 million) and trachoma (2 million), as well as those with near vision impairment caused by untreated presbyopia (826 million) ^{1 2} .

¹ WHO, Blindness and visual impairment, February 26, 2021 https://www.who.int/en/news-room/fact-sheets/detail/blindness-and-visual-itnpairment ² Vision Loss Expert Group of the Global Burden of Disease Study. Causes of blindness and vision impairment in 2020 and trends over 30 years: evaluating the prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight. Lancet Global Health 2020. doi.org/10.1016/S2214-109X(20)30489-7 i,

Furthermore, “in terms of regional differences, it is estimated that in low- and middle-income regions, the prevalence of visual impairments affecting distance vision is four times greater than in high-income regions. For near vision, rates of untreated visual impairment are estimated to exceed 80% in western, eastern and central sub-Saharan Africa, while comparative rates in high-income regions North America, Australasia, Western Europe and Asia-Pacific would be less than 10%” ³ .

Global Blindness Data reveals that there were 37.9 million blind people in the world in 2004 ⁴ . This number continues to grow. Age-related macular degeneration (AMD) is a leading cause of blindness in older adults ⁵ . This anomaly is an eye disease which results from a gradual deterioration of the macula, a small area located in the center of the retina which allows us to see details and colors with precision. This degeneration is a macular pathology due to aging, from the age of 50, leading to a progressive or rapid loss of central vision.

It is of “multifactorial, genetic and acquired origin (smoking and diet for example). The early stages known as MLA (Age-related maculopathy) include alterations of the pigment epithelium such as hypo- or hyperpigmentation and drusen and are not responsible for significant impairment of visual function. The late stages known as AMD (Age-related macular degeneration) correspond to exudative forms (wet or neovascular) and atrophic forms (dry), responsible for severe alterations in central vision. According to studies, the prevalence of exudative AMD represents 35 to 65% of late stages.

Exudative AMD is characterized by the proliferation of choroidal new vessels that cross Bruch's membrane and develop beneath the epithelium ³ Vision Loss Expert Group of the Global Burden of Disease Study. Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the Global Burden of Disease Study. Lancet Global Health 2020. dol: 10.1016/S2214-109X(20)30425-3.

⁴ B. Thylefors, A.-D. Négrel, R. Pararajasegaram, KY Dadzie, Global data on blindness. Community Eye Health Vol 1 No 12004 ⁵ Zampatti S., Ricci F., Cusumano A., Marsella LT., Novelli G., Giardina E. Review of nutrient actions on age-related macular degeneration. Nutr. Res. 2014;34:95-10S. doi: 10.1016/j.nutres.2013.10.011.

j pigmentary or in the subretinal space. There are particular forms of new vessels in exudative AMD, including:

• chorio-retinal anastomoses, also called type 3 neovascularization. This is an anastomosis between the retinal and choroidal capillary network, the origin of which is debated;

• idiopathic polypoidal vasculopathies are linked to the formation of an abnormal vascular network of choroidal origin which develops under the retinal pigment epithelium, ending in polypoidal dilations. These lesions are the cause of serohemorrhagic retinal and pigment epithelium detachments located preferentially inter-papillo-macularly.

Atrophic AMD is the advanced form of non-exudative AMD. One or more areas of atrophy of the pigment epithelium and/or the choriocapillaris membrane are observed more or less associated with drusen (accumulation of lipid deposits under the pigment epithelium and in Bruch's membrane) and abnormalities of the pigment epithelium. Atrophy may also be associated with neovascularization. » ⁶

According to a retrospective study carried out at the Douala General Hospital in Cameroon from January 1990 to December 2007 relating to the analysis of the files of all patients aged at least 40 years who consulted in the ophthalmology department, "the prevalence of low vision and blindness due to AMD is 24.3% and 5.3% respectively. The atrophic form is the most common 74.6%. In 66.7% of exudative forms, a hemorrhagic complication is revealed. » ⁷

People with AMD, as well as those with high myopia and chronic glaucoma, are at greater risk of developing cataracts. The same applies to diabetic people whose blood sugar levels are not controlled by treatment, people who live in very sunny regions or at altitude (the ⁶ Age-related macular degeneration: diagnostic and therapeutic management , HAS-June 2012, p23 ⁷ Beleho, D., Nyouma, E., Omgbwa E, A., Ellong, A., & Ebana M, G (2017). : Hospital Study in Douala HEALTH SCIENCES AND DISEASE, 18(2 Suppl).

Λ ultraviolet rays accelerate the aging of the lens) and those who have had eye trauma, eye surgery or cancer radiotherapy ⁸ . Cataract, whether senile, secondary, traumatic or congenital as in certain children, when not treated appropriately, can actually cause blindness.

Diabetic retinopathy, one of the proven causes of blindness, exists in 95% of type 1 diabetics and in 60% of type 2 diabetics after 15 years of diabetes. Unfortunately, it still represents to this day the leading cause of blindness and low vision in the working population (before the age of 50). 2% of diabetics are blind and 10% are visually impaired. ⁹

Currently, there are several methods of treatment for wet AMD, diabetic retinopathy, retinal vein occlusion, and various macular edemas: intravitreal injections, photodynamic therapy, and surgical laser.

Intravitreal injections are done directly inside the eye. Using a very fine needle inserted through the white of the eye, anti-growth factor or anti-VEGF drugs such as Lucentis (ranibizumab) or aflibercept (Eylea) are injected. The major disadvantage of this treatment is the high risk of complications. An eye infection, inflammation, and even retinal tear or detachment could occur following one of these injections;

Bevacizumab (AVASTIN), initially designed for the treatment of certain cancers and not authorized in ophthalmology, is however used as an alternative in the treatment of AMD; ¹⁰

Photodynamic therapy consists of the injection no longer into the eye but intravenously of a substance, verteprofin, which becomes toxic under the effect of a red beam and causes the destruction of blood vessels. To avoid * https://www.vidal.fr/entreprises/veux/cataracte/causes-Drevention.html ⁹ https://www.arradv.fr/comprendre-deficiences-visuelles/retinopathie-diabetique/ ¹⁰ Temporary recommendation of use (RTU) of AVASTiN in AMD in its neovascular form, Patient monitoring protocol, ANSM, September 2015 }»· certain complications, protective glasses must be worn for the 48 hours following this treatment.

Surgical laser is another possible form of treatment for AMD, retinopathy, and several retinal diseases. To prevent the new blood vessels from creating hemorrhage in the macula, the laser beam destroys them. Unfortunately, it is known that laser surgery does not improve vision, but it can slow the progression of the disease. But possible risks include inadequate correction, decreased best corrected visual acuity, transient light sensitivity, corneal opacity, and many others. ^{11 12}

Monitoring is necessary after each injection into the eye due to the high risk of complications. The same is true following surgical laser treatment or dynamic phototherapy.

These different treatments which require a cutting-edge technical platform not available in most of our sub-Saharan African countries are not only very expensive and therefore not within the reach of low-income people, but also lead to high risks of complications. some of which can lead to total loss of vision, blindness, which is really to be feared. The eyes are very precious organs, but also very complex and very sensitive. We must provide them with care devoid of any risk.

The eye health supplement of the present invention is capable of preventing and assisting in the treatment of age-related macular degeneration (AMD), cataracts, diabetic retinopathy, glaucoma, as well as various other retinal diseases. This food supplement is very effective and can be consumed every day for more than 5 years without side effects, without danger and at low cost. These different eye diseases have several common causes, including deficiencies, most of which can be corrected by our food supplement. The eyes need many vitamins and nutrients ¹¹ https://www.vidal.fr/entreprises/veux/degeneration-maculaire-dmla/traitement.html ¹² Pop magazine, February 2, 2017, Eye surgery and risks involved, Dr Michel Pop, Ophthalmologist ·» to function properly. Any deficiency is likely to cause dysfunctions which could lead to ophthalmological diseases and even blindness.

The food supplement of the invention is a concentrate of nutrients in the form of a tablet or capsule composed of Lutein, Zeaxanthin, Astaxanthin, Vitamin C, Vitamin E, Zinc in the form of zinc oxide, Copper in the form of copper oxide and possibly excipients such as silica dioxide and magnesium stearate. These food supplements are administered orally. Playing a proven role in maintaining normal vision ¹³ , they are likely to reduce the risks of cataracts ¹⁴ , diabetic retinopathy ¹⁵ , glaucoma ¹⁶ , damage to the eye with regard to ultra-radiation. violet ^17,18 , reduction in visual acuity ^{19 20 21} , and many other eye ailments.

Multiple research and clinical studies on the impact of these components have given rise to hundreds of scientific publications in world-renowned journals that can easily be found on pubmed, Embase, Web of science, and Cochrane. These scientific publications attest to the effectiveness of these nutrients on eye health.

Researchers have linked eye-healthy nutrients such as lutein and zeaxanthin, vitamin C, vitamin E and zinc to reducing the risk of some serious eye diseases like age-related macular degeneration. and cataracts. ^{20.21 19} https://www.laboratoire-lescuver.com/nos-actif/luteine-et-zeaxanthine ¹⁴ https://www.allaboutvision.com/fr-ca/sante-oeil/nutrition/luteine/ ¹⁵ Scanlon G, Connell P, Ratzlaff M, Foerg B, McCartney D, et al. Macular pigment optical density is lower in type 2 diabetes, compared with type 1 diabetes and normal contrais. Retina. 2015:35:1808-16 ¹⁶ Neacu A. & al. Neuroprotection with carotenoids in flaucoma. Oftalmologia. 2003;59(4):70-5 ¹⁷ Julie Mares. Lutein and zeaxanthin isomers in eye health and disease. 2016 Jul 17; 36:571-602 ¹⁸ Landrum JT, Bone RA. Mechanistic evidence for eye diseases and carotenoids. In Krinsky NI, Mayne ST, Sies H, editors. Crotenoids in health and disease. New Yofk: Marcel Dekker 2004:445-72 ¹⁹ Rong Liu, Tîang Wang, Bao Zhang, Li Qin, Changrui Wu, Qingshan Li, Le Ma. Lutein ans zeaxanthin supplementation and association with Visual function in age-related macular degeneration. Investigative Ophthalmology & Visual Science (IOVS). January 2015, Vol.56, 252-258. doi:https://doi.org/10.1167/iovs.l415553 ²⁰ Diet and Nutrition | AOA-American Optometry Association, https://www.aoa.org > healthy-eyes > caringfor-your-eyes ²¹ Rong Liu, Tiang Wang, Bao Zhang, Li Qin, Changrui Wu, Qingshan Li, Le Ma. Lutein ans zeaxanthin supplementation and association with visual function in age-related macular degeneration. Investigative

Around 850 carotenoids have been distinguished in nature ²² . Of these, 20 to 30 have been identified in human blood and tissues, but only lutein and zeaxanthin are present in the eye ²³ . A multitude of research studies and clinical studies have proven the effectiveness of these two elements in the preventive and curative treatment of 5 AMD ²⁴ . Lutein, zeaxanthin and meso-zeaxanthin, three antioxidants ^25,26 which are natural carotenoids, have been shown to be present in large quantities in the macula, in the center of the retina of the eye and in the lens ^{27, 28} .

Lutein and zeaxanthin cannot be produced by the body ²⁹ . They can only be supplied to the human body through food. Meso-zeaxanthin 10 on the other hand is not found in common foods, but is derived solely from lutein present in the retina ^30,31 . In the retina, these three compounds present different dominances with meso-zeaxanthin predominating at the epicenter, zeaxanthin at the mid-periphery and lutein at the periphery of the macula. ³² This macula, central part of the retina, is a layer of photosensitive cells on the back wall 15 of the eyeball. In the eye, lutein and zeaxanthin function as a screen

Ophthalmology & Visual Science (IOVS). January 2015, Vol.56,252-258. doi:https://doi.org/10.1167/iovs.l415553 ²² Maoka T. Carotenoids as natural functional pigments. J.Nat. Med. 2020; 74:1-16. doi: 10.1007/sll418019-01364-x.

²³ Bronwyn Eisenhauer, Sharon Natoli, Gerald Uew, and Victoria M. Flood, Lutein and Zeaxanthin—Food Sources, Bioavailability and Dietary Variety in Age-Related Macular Degeneration Protection, doi: 10.3390/nu9020120 2017 Feb 9 ²⁴ Uwen Feng, Kailai Nie, Hui Jiang, Wei Fan. Effects of lutein supplementation in age-related macular degeneration. Published: December 30,2019 https://doi.org/10.1371/journal.pone.0227048 ²⁵ Krinsky NI. Antioxidant function of carotenoids. Free Radie Biol Med. 1989; 7:617-635.

²⁶ Schalch W. Carotenoids in the retina: a review of their possible role in preventing or limiting damage caused by light and oxygen. Emeritl ChanceB eds. Free Radicals and Aging. 1992;280-298.Birkhauser Verlag Basel, Switzerland.

²⁷ Carotenoids: Health Effects, SA Tanumihardjo, in Encyclopedia of Human Nutrition (Third Edition), 2013 ²⁸ SnodderlyDM. Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins (review). Am J Clin Nutr. 1995;62(suppl)1448S-1461S.

²⁹ Retinitis Pigmentosa and Allied Disorders, Andrew P. Schachat MD, in Ryan's Retina, 2018 ³⁰ Bhosale P, Serban B, Zhao DY, Bernstein PS. Identification and metabolic transformations of carotenoids in ocular tissues of the Japanese quail Coturnix japonica. Biochemistry 2007; 46:9050-9057.

³¹ Johnson EJ, Neuringer M, Russell RM, Schalch W, Snodderly DM. Nutritional manipulation of primate retinas, III: Effects of lutein or zeaxanthin supplementation on adipose tissue and retina of xanthophyll-free monkeys. Invest Ophthalmol Vis Sci 2005; 46 (2): 692-702.

³² Nolan JM, Meagher K., Kashani S., Beatty S. What is meso-zeaxanthin, and where does it corne from? Eye. 2013; 27:899-905. doi:10.1038/eye.2013.98.

“natural solar which absorb excess light energy, thus protecting the eyes against harmful blue light ³³ .

According to a study carried out on 36,644 American male subjects between 45 and 75 years old, over 8 years, researchers observed a 19% reduction in the risk of cataracts 5 associated with high intakes of lutein and zeaxanthin but not with other carotenoids such as alpha carotene, beta carotene, lycopene, betacryptoxanthin or with vitamin A ³⁴ . Lutein and zeaxanthin can therefore reduce the risk of developing severe cataracts. Similar findings were obtained in a study of 77,466 nurses aged 45 to 71. ³⁵

There is currently no recommended dietary allowance (RDA) for lutein or zeaxanthin, but there is strong evidence that lutein consumption is safe up to 20 mg/day ³⁶ . Several epidemiological studies carried out with doses of lutein varying from 8 to 40 mg/day over a period ranging from 7 days to 24 months have shown no side effects. Lutein can be safely consumed every day for over 6 years. ³⁷

According to toxicological evaluations, "Based on the metabolic profiles and the absence of evidence of adverse effects following administration to humans and animals of high doses of lutein and zeaxantin, the Acceptable Daily Intake (ADI) established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) for lutein extracted from tagetes erecta, i.e. between 0 and 2 ³³ The Photobiology of Lutein and Zeaxanthin in the Eye, Joan E . Roberts* and Jessica Dennison, doi: 10.1155/2015/687173, Published online 2015 Dec 20 ³⁴ Brown l, Rimm EB, Seddon JM, Giovannucci EL, Chasan-Taber L, Spiegelman D, Willett WC, Hankinson SE. A prospective study of carotenoid intake and risk of cataract extraction in US men. Am J Clin Nutr. 1999 Oct;70(4):517-24.

³⁵ Chasan-Taber L, Willett WC, Seddon JM, Stampfer MJ, Rosner B, Colditz GA, Speizer FE, Hankinson SE. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. Am J Clin Nutr. 1999 Oct;70(4):509-16.

³⁶ https://lizengo.fr/faa/combien-de-mg-de-luteine-dois-ie-prendre-par-iour/ ³⁷ Katherine M. Ranard, Sookyoung Jeon, Emily S. Mohn, James C. Griffiths, Elizabeth J. Johnson and John W. Erdman, Jr., Dietary guidance for lutein: consideration for intake recommendations is scientifically supported, Eur J Nutr. 2017; 56(Suppl 3): 37-42. PMCID: PMC5715043, PMID: 29149368, Published online 2017 Nov 17. doi: 10.1007/S00394-017-1580-2

X mg/kg body weight is considered an appropriate and conservative guideline” ³⁸ .

“The joint FAO/WHO expert committee (JECFA, 2006b and 2006c) has examined xanthophylls on several occasions and proposed an ADI for lutein (extracted from Tagetes erecta) of 0 to 2 mg/kg of weight body weight/day, value based on a NOAEL of 200 mg/kg body weight/day and a safety factor of 100. For a 60 kg person, this would mean that there would be no adverse effects for a daily intake of lutein 120 mg. » ³⁹

The National Eye Institute in the United States, through the AREDS (Age Related Eye Disease Study) followed 3,640 patients for more than 6 years. Sufficient lutein intake has been shown to improve recovery from glare, contrast sensitivity and visual acuity ⁴⁰ . People who consumed an equivalent of 30 mg of lutein per day for a period of 140 days demonstrated an increase of 21 to 39% in retinal pigment density. ⁴¹

It is widely demonstrated that appropriate consumption of foods containing vitamin A, lutein, zeaxanthin such as green vegetables and brightly colored fruits helps optimize eye health and function throughout life. Some of these foods are presented in the table below with their proportions of lutein and zeaxanthin.

³⁸ Archived - Information on novel foods - Canada.ca https://www.canada.ca/en/healthcanada/services/food-nutrition/genetically-modified-foods-other-novel-foods/approved-products/added-juices- luteine-crystalline-floraglo.html#shr-pgO ³⁹ Higher Health Council, Belgium, Opinion n* 8592, Revision of recommendations concerning additional intake of lycopene and lutein in food supplements, December 2, 2009, p.7 ⁴⁰ A randomized, placebo controlled, clinical trial of high dose supplementation with vitamins C and E and beta carotene for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001 Oct;119(10):1417-36.

⁴¹ Landrum JT, Bone RA, Joa H, Kilburn MD, Moore LL, and Sprague KE. A one year study of the macular pigment: the effect of 140 days of a lutein supplement. Exp Eye Res. 1997 Jul; 65(1):57-62.

4” .4

Individual lutein and zeaxanthin values of common foods ⁴²

'Food'·:·· ·J Euteinetrans ·(ug/ioœg).j Zéàxàrithine tràüs.(gg/i()Q gj'i Red apple with skin 15 0 — Dried apricot 0 0 — Artichoke heart 62 18 3.4 Cooked asparagus 991 0 — cooked broccoli 772 0 — Cooked Brussels sprouts 155 0 — Red cabbage 0 0 — Raw cantaloupe 19 0 — Coriander 7703 0 — Cucumber 361 0 — Endive 399 3 133.0 Green grapes 53 6 8.8 Red grapes 24 4 6.0 Frozen Cooked Green Beans 306 0 — Honeydew 25 0 — Cooked kale 8884 0 Kiwi 171 0 Iceberg lettuce 171 12 14.3 Romaine lettuce 3824 0 — Cooked Lima Beans 155 0 — Mango 6 0 — Nectarine 8 4 2.0 Green olive 79 0 Orange juice 33 26 1.3 Parsley 4326 0 — Canned peach 0 8 — Raw peach 11 3 3.7 Green pepper 173 0 — Orange pepper 208 1665 0.1 Red pepper 0 22 0.0 Yellow pepper 139 18 7.7 Raw green onions 782 0 — Green onions cooked in oil 2488 0 cooked spinach 1264 0 — Raw spinach 6603 0 —

⁴² Perry A., Rasmussen H., Johnson E. Xanthophyll (lutein, zeaxanthin) content in fruits, vegetables and corn and egg products. J.Food Comp. Anal. 2009; 22:9-15. doi: 10.1016/j.jfca.2008.07.006.

μ*

Raw acorn squash without skin 47 0 — Cooked buttemut squash 57 0 — Cooked yellow squash 150 0 — Raw tomato 32 0 — Watermelon 4 0 — Zucchini cooked with skin 1355 0 — Cooked corn 202 202 1.0 Raw pistachios 1405 0 - Whole cooked egg 237 216 1.1 Cooked egg yolk 645 587 1.1 Whole raw egg 288 279 1.0 Raw egg yolk 787 762 1.0

The bioavailability of lutein and zeaxanthin in ocular tissue depends on their absorption from consumed foods ^43,44 · ^{43 44 45} , which is influenced by many other factors. It is clear that the quantity of food to be consumed to obtain the appropriate proportion of lutein and zeaxantin is enormous and well beyond the daily capacity of the stomach. We cannot therefore eat exclusively these foods, at the risk of suffering deficiencies in other essential vitamins and nutrients that the body needs on a daily basis, which would strongly and very detrimentally alter the overall health of the body. body. It is for this purpose that supplementation with the food supplement of the invention proves essential to obtain the optimal quantity of these carotenoids. Zeaxanthin can be consumed in appropriate proportion every day for more than 8 years without side effects and without harm. ⁴⁶

Astaxanthin is a powerful antioxidant from the carotenoid family known for a multitude of pharmacological effects ⁴⁷ . Its effectiveness for ⁴³ Bohn T. Bioavailability of non-provitamin A carotenoids. Curr. Nutr. Food Sci. 2008; 4:240-258. doi:10.2174/157340108786263685.

⁴⁴ van Het Hof KH, West CE., Weststrate JA, Hautvast JG Dietary factors that affect the bioavailability of carotenoids. J.Nutr. 2000; 130:503-506. doi: 10.1093/jn ⁴⁵ Castenmîller JJ., West CE. Bioavailability and bioconversion of carotenoids. Annu. Rev. Nutr. 1998; 18:1938. doi: 10.1146/annurev.nutr.l8.1.19.

⁴⁶ Age-Related Eye Disease Study 2 Research G Lutein+zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the age-related eye disease study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309:2005-2015. doi:10.1001/jama.2013.4997.

⁴⁷ Alugoju P, Krishna Swamy VKD, Anthikapalli NVA, Tencomnao T. Health benefits of astaxanthin against age-related diseases of multiple organs: A comprehensive review. PMID: 35708049 doi: 10.1080/10408398.2022.2084600 retina, age-related macular degeneration, ocular surface disorders, uveitis, cataract and asthenopia are reported in many studies. ^48,49,50,51

Astaxanthin is the subject of more than 3,055 scientific publications ^{43 * * * * * * * 51 52 * 54 55} . Although it is a carotenoid in the same way as lycopene from tomatoes and beta-carotene from 5 carrots, it is not found in vegetables as is the case for lutein and zeaxanthin, but mainly in living organisms. underwater, crustaceans such as shrimp, algae such as haematococcus pluvialis, salmon, rainbow trout, yeast, certain fish and various other seafood. These underwater organisms must their color comes from the pigment astaxanthin.

Like lutein and zeaxanthin, astaxanthin is not produced in the human body yet it is a crucial nutrient for health. It is a powerful antioxidant, one of the most powerful that our God has placed in nature. Its ability to fight free radicals is 6,000 times greater than that of vitamin C, 100 times greater than that of vitamin E and 40 times greater than that of beta-carotene ^53,54,55 .

These antioxidant properties are responsible for its multiple beneficial effects on health in general, and eye health in particular.

The retina is the innermost nerve layer of the eye and sensitive to light. It is the most metabolically active tissue in the body, with a consistently high demand ⁴³ Wei-Ning Lin, Kishan Kapupara, Yao-Tseng Wen, Yi-Hsun Chen, l-Hong Pan and Rong-Kung Tsaî.

Haematococcus pluvialis-Derived Astaxanthin is a Potential Neuroprotective Agent against Optic Nerve

Ischemia ⁴⁹ Harada F., Morikawa T., Lennikov A., Mukwaya A., Schaupper M., Uehara O., Takai R., Yoshida K., Sato J.,

Horie Y., et al. Protective Effects of Oral Astaxanthin Nanopowder against Ultraviolet-induced Photokeratitis in Mice. Oxid. Med. Cell. Longev. 2017,-2017:1956104. doi:10.1155/2017/1956104.

⁵⁰ Otsuka T., Shimazawa M., Inoue Y., Nakano Y., Ojino K., Izawa H., Tsuruma K., Ishibashi T., Hara H.

Astaxanthin Protects Against Retinal Damage: Evidence from In Vivo and In Vitro Retinal Ischemia and Reperfusion Models. Curr. Eye Res. 2016;41:1465-1472. doi:10.3109/02713683.2015.1127392.

⁵¹ Otsuka T., Shimazawa M., Nakanishi T., Ohno Y., Inoue Y., Tsuruma K., Ishibashi T., Hara H. Protective effects of a dietary carotenoid, astaxanthin, against light-induced retinal damage. J. Pharmacol. Sci. 2013;123:209218. doi: 10.1254/jphs.l3066FP.

^H https://pubmed.ncbi.nlm.nih.gov/?term=astaxanthin accessed October 18, 2022 ^M Vyshnavy Balendra, Sandeep Kumar Singh. Therapeutic potential of astaxanthin and superoxide dismutase in Alzheimer's disease, Open Biol. 2021 Jun; 11(6): 210013. PMCID: PMC8241491 - PMID: 34186009 - June 30, 2021. doi: 10.1098/rsob,210013 ⁵⁴ Goto S, Kogure K, Abe K, Kimata Y, Kitahama K, Yamashita E, Terada H. 2001 . Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Biochem. Biophys. Acta 1512,251-258. (10.1016/50005-2736(01)00326-1) ⁵⁵ Nishida Y, Yamashita E. 2007. Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen using chemiluminescence detection System. Carotenoid Sci. 11.16-20.

'3 in oxygen and almost continuous exposure to light. Both conditions lead to vulnerability of the eyes to oxidative damage initiated by irradiation and resulting inflammation. Retinal ganglion cell death is a common feature of many retinal disorders such as glaucoma, optic neuropathies, diabetic retinopathy, and AMD. The majority of these conditions are characterized by oxidative stress, ischemia and apoptosis as the main pathogenic factors. Several preclinical and clinical evidence supports the use of astaxanthin, vitamin C and vitamin E in the prevention and treatment of eye diseases that can lead to visual defects or even complete loss of vision.

Recommended or approved doses for supplementation containing astaxanthin vary by country. They are between 2 and 24 mg/day ^{ss 56} of astaxanthin. At the request of the European Commission, the FEEDAP scientific group of the EFSA (European Food Safety Authority) assessed the safety of astaxanthin derived from the microalga Haematococcus pluvialis as part of an application submitted under Regulation (EC ) No. 258/1997, and more particularly when it is used as an active element in food supplements. In the assessment made in 2019, the FEEDAP scientific group established an acceptable daily intake (ADI) of 0.2 mg astaxanthin/kg body weight. ⁵⁷

Vitamin C reduces the risk of developing cataracts and when taken in combination with other essential nutrients, it can slow the progression of age-related macular degeneration and loss of visual acuity. It is also proven that ^ss Thomas Brendler, Elizabeth Mary Williamson. Astaxanthin: How much is too much? A safety review PMID: 31788888 DOI: 10.1002/ptr,6514 ⁵⁷ EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA); Dominique Turck, Jacqueline Castenmiller, Stefaan de Henauw, Karen Ildico Hirsch-Ernst, John Kearney, Alexandre Maciuk, Inge Mangelsdorf, Harry J McArdle, Andronîki Naska, Carmen Peiaez, Kristina Pentieva, Alfonso Siani, Frank Thies, Sophia Tsabouri, Marco Vinceti, Francesco Cubadda, Karl-Heinz Engel, Thomas Frenzel, Marina Heinonen, Rosangela Marchelli, Monika Neuhauser-Berthold, Morten Poulsen, Yolanda Sanz, Josef Rudolf Schlatter, Henk van Loveren, Reinhard Ackerl, Wolfgang Gelbmann, Hans Steinkellner, Helle Katrine Knutsen. Safety of astaxanthin for its use as a novel food in food supplements - PMID: 32874213 - PMCID: PMC7448075 - DOI: 10.2903/j.efsa.2020.5993!?

Vitamin E protects eye cells against unstable molecules called free radicals, which break down healthy tissue. ⁵⁸

According to a scientific publication published in the American Journal of Clinical Nutrition, vitamin C supplementation over a long period of time, 10 years, reduces the risk of cataracts. The researchers who made this publication looked at the link between nutrition and two types of cataract with different locations, the cortical cataract (whose opacity is initially limited to the coating layers of the lens, thus sparing the nucleus) and the posterior subcapsular cataract (the opacity of which is initially limited to a layer immediately in contact with the posterior capsule of the lens). Taking vitamin C supplements at a dose of 362 mg or more per day in women under 60 years of age was associated with a 57% reduction in the risk of developing cortical cataracts compared to a dose of 140 mg per day. Additionally, supplementation for more than ten years was linked to a 60% reduction compared to no supplementation. ⁵⁹

Several scientific publications report a real effect of the consumption of vitamin C as well as vitamin E in reducing the risk of contracting cataracts ⁶⁰ . Significant evidence has been presented in these publications. Dose-response analysis indicated that an increase in vitamin C consumption by 500 mg/day was significantly associated with an 18% decrease in cataract risk. And any increase in lutein or zeaxanthin consumption of lOmg/day reduces the risk of contracting cataracts by 26%. Likewise, it has been shown in these various studies that the risk of contracting cataracts decreases by ⁵⁸ American Optometry Association, Diet and nutrition https://www.aoa.org/healthv-eves/ca ring-for-voureves/diet- and-nutrition?sso=v, accessed 16/10/2022 ⁵⁹ Taylor A, Jacques PF, Chylack LT, Jr, Hankinson SE, Khu PM, Rogers G, Friend J, Tung W, Wolfe JK, Padhye N, Willett WC . Long-term intake of vitamins and carotenoids and odds of early age-related cortical and posterior subcapsular lens opacifications. American Journal of Clinical Nutrition, Vol. 75, No. 3,540-549, March 2002.

“JIANG, H. YIN, Y. WU, CR. « and col. » Dietary vitamin and carotenoid intake and risk of age-related cataract. American Journal of Clinical Nutrition, 2019,109, p. 43-54 (doi: 10.1093/ajcn/nqy270).

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10% among the biggest consumers of vitamin E. ^61,62,63,64 '65, ^66,67 . Known to improve visual performance, these vitamins and nutrients limit eye fatigue, prevent the risk of AMD and cataracts and limit their progression.

Zinc plays an essential role in transporting vitamin A from the liver to the retina to produce melanin, a protective eye pigment. Impaired vision, such as poor night vision and cloudy cataracts, has been linked to zinc deficiency ^{61 62 * 64 * 66 67 68} .

“The concentration of zinc in the retina is high. Zinc plays a very important role in antioxidant defense mechanisms as it acts as a cofactor of superoxide dismutase and is involved in the regulation of catalase.

Zinc is also a cofactor of retinol dehydrogenase which is involved in the metabolism of visual pigments as well as in the metabolism of retinol binding protein transporting vitamin A” ⁶⁹

Eyes with AMD experience reduced proportions of retinal pigment epithelium 15 and reduced levels of zinc and copper in the choroid complex ⁷⁰ , further compromising retinal health. Oral supplementation ⁶¹ Tan AG, Mitchell P, Fiood VM, Buriutsky G, Rochtchina E, Cumming RG, Wang JJ. Antioxidant nutrient intake and the long-term incidence of age-related cataract: the Blue Mountains Eye Study. American Journal of Clinical Nutrition. 2008; 870:1899-905 ⁶² Christen WG, Liu S, Glynn RJ, Gaziano JM, Buring JE. Dietary carotenoids, vitamins C and E, and risk of cataract in women: a prospective study. Arch Ophthalmol. 2008; 126:102-9.

^eî Lyle BJ, Mares-Perlman JA, Klein BE, Klein R, Greger JL Antioxidant iritake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study. Am J Epidemiol. 1999; 149:801-9.

⁶⁴ Jacques PF, Chylack LT Jr, Hankinson SE, Khu PM, Rogers G, Friend J, Tung W, Wolfe JK, Padhye N, Willett WC et al. Long-term nutrient intake and early age-related nuclear lens opacifications. Arch Ophthalmol. 2001; 119:1009-19.

^es Taylor A, Jacques PF, Chylack LT, Khu PM, Rogers G, Friend J, Tung W, Wolfe JK, Padhye N, Willett WCet al. Long-term intake of vitamins and carotenoids and odds of early age-related cortical and posterior subcapsular lens opacifications. Am J Clin Nutr. 2002; 75:540-9.

⁶⁶ Yoshida M, Takashima Y, Inoue M, Iwasaki M, Otani T, Sasaki S, Tsugane S; JPHC Study Group. Prospective study showing that dietary vitamin C reduced the risk of age-related cataracts in a middle-aged Japanese population. Eur J Nutr. 2007; 46:118-24.

⁶⁷ Mares JA, Voland R, Adler R, Tinker L, Millen AE, Moeller SM, Blodi B, Gehrs KM, Wallace RB, Chappell RJ et al. Healthy diets and the subsequent prevalence of nuclear cataract in women. Arch Ophthalmol. 2010;128:738-49.

⁶⁸ https://www.aoa.org/healthy-eyes/caring-for-your-eyes/diet-and-nutrition?sso=y ⁶⁹ Age-related macular degeneration and its prevention: the rise of micronutrition, the Thesis for State Diploma of Doctor of Pharmacy by Cindy BINOT, May 2, 2013 ^TO Jay C Erie, Jonathan A Goodjohn A Butz, José S Pulido. Reduced zinc and copper in the retinal pigment epithelium and choroid in age-related macular degeneration, PMID: 18848316, DOI: 10.1016/j.ajo.2008.08.014

Μ •T .•'J zinc and copper reduces the risk of progression of AMD and promotes overall retinal health.

Several clinical trials have established that zinc supplementation of 80 mg/day reduces the risk of progression of advanced AMD in patients who already have large drusen, without any particular side effects. . ^71,72,73

Zinc reduces the amount of copper absorbed by the human intestine and large doses of zinc can cause copper deficiency. For this reason, it is essential to always combine copper with any zinc supplementation.

With reference to the description developed above and as an example of formulation, each tablet or capsule of the food supplement of the invention intended for eye health is composed of:

• 6.5 mg of lutein extracted from marigold;

• 1.3 mg of zeaxanthin extracted from marigold;

• 2 mg of astaxanthin extracted from the microalgae haematococcus pluvialis;

• 175 mg of vitamin C in the form of ascorbic acid;

• 60 mg of vitamin E in the form of d-alpha tocopheryl acetate;

• 25 mg of zinc in the form of zinc oxide;

• 360 pg of copper in the form of copper oxide;

• Those skilled in the art will be able to add an appropriate proportion of excipients such as silica dioxide and magnesium stearate or any other having similar characteristics.

The active molecule titration of each nutrient must be carefully controlled by HPLC (high performance liquid chromatography) or any other appropriate laboratory equipment.

⁷¹ Newsome, DA., Swartz, M., Leone, NC., Elston, R. and Miller, E. Oral zinc in macular degeneration. Arch Ophthalmol. 1988,106,pp. 192-198.

⁷² AREDS - USA National Eye Institute, Age-Related Eye Disease Study (AREDS, Sept 1990-Dec 2006), https://clinicaltrials.gov/ct2/show/NCT00000145 ⁷³ AREDS 2 - USA National Eye Institute, Age-Related Eye Disease Study (AREDS 2, Sept 2006-Oct 2012), https://clinicaltrials.gov/ct2/show/NCT00345176

Those skilled in the art will ensure the conformity of the nutrients on a microbiological level. In addition, he must ensure that all the nutrients he uses are non-GMO, allergen-free, and respect the safety threshold doses of heavy metals (lead, mercury, arsenic, chromium, etc.).

Those skilled in the art will be able to calculate the proportions of plant extracts and dry matter extracts according to their active molecule titers in order to produce tablets or capsules offering the best guarantees of quality and safety. , formulation, homogeneity, uniformity, conformity, activity, and stability. Manufacturing must take place in a space suitable and reserved for the execution and control of preparations meeting the conditions of Good Preparation Practices in accordance with standards. Furthermore, he will be able to modify the formulation if necessary in order to comply with the regulatory and normative requirements in force at the time of manufacture.

For better effectiveness of the food supplement of the invention, it is important to remember the need to avoid factors that aggravate eye diseases, in particular:

• smokers are two to three times more likely to develop AMD ^74,75 and other eye diseases. You have to stop smoking;

• sugar, like tobacco, is a worst enemy of eyesight. Excess sugar strongly promotes cataracts, AMD, diabetic retinopathy and even blindness;

• alcohol accelerates the aging of cells in the body. And for the eyes, this can lead to one or other of the eye diseases due to damage to the cornea or retina: premature AMD, cataracts, glaucoma. ^{74 7 76 74} THORNTON, J., R. EDWARDS, P. MITCHELL, RA. HARRISON, I. BUCHAN and SP. KELLY. Smoking and age-related macular degeneration: a review of association. Eye; flight. 19, no. 9, 2005, p. 935-944.

^7S CHAKRAVARTHY, U., TY. WONG, A. FLETCHER, E. PIAULT, C. EVANS, G. ZLATEVA, R. BUGGAGE, A. PLEIL and P. MITCHELL Clinical risk factors for age-related macular degeneration: a systematic review and metaanalysis. BMC Ophthalmology, December 13, 2010; flight. 10, p. 31 ⁷⁶ https://icrcat.com/fr/abuser-de-lalcool-entraine-une-relaxation-musculaire-qui-affecte-notre-vision/ isf η

• chronic exposure to blue light, such as that emitted by LED screens and certain household lighting, increases the risk of developing AMD and several eye diseases. Blue light attacks the retina without short-term consequences on vision, but with fairly concrete long-term risks. ⁷⁷ The same is true of the ultraviolet rays of sunlight;

• complications of cardiovascular diseases seem to increase the risk of developing AMD ⁷⁸ . Blood cholesterol levels and blood pressure must be controlled.

⁷⁷ https://oeil-bleu.com/blogs/iumiere-bleue/lumiere-bleue-dmla ⁷⁸ Sonia Mehta, MD, The MSD Manual, Age-related macular degeneration (AMD), Vitreoretinal Diseases and Surgery Service, Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University

Claims (6)

1. Food supplement for eye health composed of Lutein, Zeaxanthin, Astaxanthin, Vitamin C, Vitamin E, Zinc in the form of zinc oxide, Copper in the form of copper oxide and possibly d excipients such as silica dioxide and magnesium stearate; 2. Food supplement according to claim 1 characterized in that it is a concentrate of nutrients in the form of a tablet or capsule capable of preventing and helping in the treatment of age-related macular degeneration (AMD); 3. Food supplement according to claim 1 characterized in that it is capable of preventing and helping in the treatment of cataracts; 4. Food supplement according to claim 1 characterized in that it is capable of preventing and helping in the treatment of diabetic retinopathy; 5. Food supplement for eye health according to claim 1, characterized in that it is capable of preventing and helping in the treatment of glaucoma and several other retinal diseases; 6. Food supplement for eye health according to all of the preceding claims, characterized in that it is very effective and capable of being consumed every day for more than 5 years without danger and without notable side effects.