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Lycium Barbarum - for Vision (Retina) | Longevity | Intestinal Health and Slows Aging!

Lycium Barbarum (LB), also known as wolfberry, has been shown to provide powerful anti-aging effects. Significantly, long term feeding of LB in lab animals have shown increased longevity, eye (retina) support, including age-related macular degeneration (AMD), support liver health and boost of intestinal health and immunity.(1)

 

  INCREASING MEAN LIFESPAN

  • Studies involving D. melanogaster (fruit fly), shown LB increases serum and organ levels of superoxide dismutase (SOD), reduced glutathione and catalase (CAT) antioxidant activity. SOD and CAT have been shown in research models to promote longevity. (2)
  • Positively promotes anti-aging pathways (MAPK, TOR, S6K) and increases expression of longevity genes (2)

PRESERVING RETINA FUNCTION

  • Retinal diseases have underlying high levels of oxidative stress. Photoreceptors and RPE (Retinal Pigment Endothelium) have very high metabolic activity and additional stress comes from photooxidative damage (due to light). Oxidative stress in the retina leads to increased amounts of lipofuscin - which is formed from oxidative by products and can trigger retinal damage and apoptosis. 
  • LB has shown potential support for retinal diseases. While most studies have been in animal models, long term studies and human studies still need to be done. Retinal diseases which may benefit from LB include (3)
    • Age-Related Macular Degeneration (AMD) - in early AMD LB has slowed progression and inhibited soft drusen formation.
    • Diabetic Retinopathy (DR) - In animal studies, LB restored retinal thickness, reversed hyperglycemic oxidative stress, promoted reductions in retinal vascular changes seen in diabetic retinopathy. Reversed increased VEGF vascular growth factor - which increases vascularization in DR. Also enhanced protection of blood-retinal-brain barrier (which is disrupted by diabetes), causing macular edema. 
    • Retinitis Pigmentosa - an inherited genetic disease of the retina. LB may improve visual processing by increasing antioxidant protection  of photoreceptors.
  • LB significant increases antioxidation levels, while inhibiting lipid peroxidation (fatty acids are prevalent in photoreceptor membranes).
  • LB is the richest source of natural Zeaxanthin. Contains very high bioavailable Zeaxanthin (demonstrated in animals and humans)

PROMOTES INTESTINE HEALTH / IMMUNE RESPONSE

  • Strengthens the intestinal barrier, which is critical for maintaining a healthy functioning intestine.LB Promotes increased production of short chain fatty acids (which is anti-inflammatory)
  • Promotes intestinal immunity (1)  Support general immune response through changes in gut microbiota  and increases in short chain fatty acids.(5)

PROTECTS LIVER 

  • Attenuates liver cell damage from environmental contaminants (plastics), in addition to alcohol toxicity by increasing levels of Nrf2, a master regulator of cellular antioxidants in the cell. As a result,  Nrf2 triggers significant increases in cellular antioxidant activity and inhibiting apoptosis of the liver cells. Alcohol induced damage to the liver is a result of increased oxidative stress and destruction of the cells.(1,6,7)

     

    VISION VITALITY  (Lycium Bararum)

     

      REFERENCES:

      (1) Ding Y, et al. Effects of long-term consumption of polysaccharides from the fruit of Lycium barbarum on host's health.  Food Res Int. 2021 Jan.

      (2) Tang R, et al. Lycium barbarum polysaccharides extend the mean lifespan of Drosophila melanogaster.  Food Funct. 2019 Jul.

      (3) Neelam K, et al. Fructus lycii: A Natural Dietary Supplement for Amelioration of Retinal Diseases. Nutrients. 2021 Jan.

      (4) Ding Y, et al. Modulating effects of polysaccharides from the fruits of Lycium barbarum on the immune response and gut microbiota in cyclophosphamide-treated mice.

      (5) Ding Y, et al. Modulating effects of polysaccharides from the fruits of Lycium barbarum on the immune response and gut microbiota in cyclophosphamide-treated mice. Food Funct. 2019 Jun.

      (6) Liu R, et al. Protective effect of Lycium barbarum polysaccharide on di-(2-ethylhexyl) phthalate-induced toxicity in rat liver. Environ Sci Pollut Res Intl. 2021. Jan.

      (7) Wang H, et al. Hepatoprotective effect of crude polysaccharide isolated from Lycium barbarum L. against alcohol-induced oxidative damage involves Nrf2 signaling. Food Sci Nutr. 2020 Oct..

      Oxidative Stress and Inflammation - Pathogenesis in Degeneration of the Retina

      Neurodegenerative diseases of the retina are mostly attributable to oxidative stress and inflammation.(1)  Diseases of the retina target the retinal epithelial cells, and photoreceptors. Photoreceptors are the processing centers in the retina, and are the primary area of vision. The retina has the highest metabolic rate of any tissue in the body. Furthermore, the retina must endure oxidative stress from chronic exposure to light, which will damage the retina. In addition, retina degeneration is associated with inflammation. The result is that with age, the retina becomes damaged, and blindness is the end effect in older people.

       

      AGE RELATED MACULAR DEGENERATION. Degeneration of retinal cells (photoreceptor and retinal pigment epitheilium (RPE) cells) by oxidative stress and inflammation is responsible for age-related macular degeneration (AMD).

      • PHOTORECEPTORS - Are comprised of rods and cones.  Are under constant threat of oxidative threats, including excessive stress from light, high oxygen requirements, All of which make photo receptors susceptible to degradation and death of the photo receptors.

      (1) Oxidative Stress - NrFT2. Cellular Transcription Factor for Endogenous Antioxidant Protective Factors

      • CARNOSIC ACID

      Carnosic Acid is an electrophilic antioxidant which crosses the blood brain barrier. Carnoisc acid is a potent activator of Nrf2, a transcription factor that causes the increased production of endogenous antioxidants. Additionally, carnoisc acid is unqiue in that it does not deplete endogenous levels of glutathionine, the key cellular antioxidant, unlike other antioxidants.(2) In a study of high intensity lighting on photooxidative damage of the retina, adding carnoisc acid to AREDS ingredients greatly increased protection of retina vs AREDS alone.(3)

      • LYCIUM BARBARIM (WOLFBERRY)

        Protects the eye and retina in multiple ways. First, lycium bararum protects the photreceptor cells from light-induced retina damage by activating Nrf2.(4)

        2) Inflammation - NLRP3 inflammasome activation is involed in the pathogenesis of AMD.

        • BLACK CURRANT / BILBERRY EXTRACT (C3G)

        C3G is considered the most important anthocyanin in maintaining health of the retina. Recently, research indicates that cyanidin-3-glucoside (C3G) has potent anti-inflammation properties and may inhibit  inflammasome damage to retinal epithelium cells.(5) C3G further reduces oxidative stress of the retina, and light induced retinal degeneration,  by activating Nrf2 endogenous levels.(6)

         

        VISION VITALITY (Carnosic Acid | Lycium Barbarum | C3G)

         

        REFERENCES:
        (1) Rohowetz RJ, et al, Reactive Oxygen Species-Mediated Damage of Retinal Neurons: Drug Development Targets for Therapies of Chronic Neurodegeneration of the Retina. Int J Mol Sci. 2018 Oct

        (2) Rezaie T, et al. Protective effect of carnosic acid, a pro-electrophilic compound, in models of oxidative stress and light-induced retinal degeneration. Invest Ophthalmol Vis Sci. 2012 Nov

        (3) Wong P, et al, Enhancing the efficacy of AREDS antioxidants in light-induced retinal degeneration.  Mol Vis. 2017 Oct

        (4)  Tang L, et al. Antioxidant effects of Lycium barbarum polysaccharides on photoreceptor degeneration in the light-exposed mouse retina. Biomed Pharmacother. 2018 Jul

        (5) Jin X, et al. Cyanidin-3-glucoside Alleviates 4-Hydroxyhexenal-Induced NLRP3 Inflammasome Activation via JNK-c-Jun/AP-1 Pathway in Human Retinal Pigment Epithelial Cells.  J Immunol Res. 2018

        (6) Wang Y, et al. Cyanidin-3-glucoside and its phenolic acid metabolites attenuate visible light-induced retinal degeneration in vivo via activation of Nrf2/HO-1 pathway and NF-κB suppression.  Mol Nutr Food Res. 2016 Jul

        Vision Longevity - Activating Nrf2 in the Retina by Lutein Zeaxanthin and Meso zeaxanthin

        It has been well studied that the carotenoids lutein and zeaxanthin play an important role in preserving eye function by directly acting as antioxidants. However, new research indicates that these powerhouses go one important step further. This is through the activation the Nfr2 antioxidant defense network.

        Nrf2 is a latent protein in the cell, that when activated, becomes a powerful transcription factor that turn on the Antioxidant Response Element (ARE). ARE is the master antioxidant switch in the cell and provides overwhelming antioxidant response, including increased levels of the potent cellular protector glutathione.

        LUTEIN ZEAXANTHIN and MESO ZEAXANTHIN act as both direct antioxidants and as Nrf2 activators. Significantly, this makes their protection capacity for the retina significantly greater than only acting as an antioxidant. Implications of this include more capacity to slow the aging of the eye and preserve vision with aging. 

        NRF2 CELLULAR PROTECTION:

        • Nrf2 Increases Glutathione Levels in Retina - Glutathione reduces toxic and age accelerating lipid and protein peroxidation in retina.
        • Mitigates Oxidative Stress. Oxidative stress is a significant factor in the disease initiation and progression of AMD (Age Related Macular Degeneration) and other diseases of the eye. Therefore, lutein, zeaxanthn and meso zeaxanthin which significantly mitigate oxidative stress, may aid in the prevention of AMD.
        • Mitigates Inflammation of the retina. Oxidative Stress activates Inflammation pathways in the retina which becomes chronic is eye diseases.
        • Meso zeaxanthin has been shown in research studies to have especially strong anti-inflammation potential.

         

        VISION VITALITY MAX (LUTEIN | ZEAXANTHIN | MESO ZEAXANTHIN)

         

        REFERENCES:

        (1) Frede K, et al. Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells. J Agric Food Chem. 2017 Jun 30

        (2) Liu H, et al. Protective effect of lutein on ARPE-19 cells upon H2O2-induced G2/M arrest.  Mol Med Rep. 2017 Jun 21.

        (3) Lima VC, et al. Macular pigment in retinal health and disease. Int J Retina Vitreous. 2016 Aug

        (4) Orhan C, et al. Mesozeaxanthin Protects Retina from Oxidative Stress in a Rat Model. Ocul Pharmocol Ther, 2016 Nov

        (5) Firdous AP. et al. Anti-inflammatory potential of carotenoid meso-zeaxanthin and its mode of action.  Pharm Biol. 2015 Jul;53(7):961-7.

        (6) Zou X, et al. Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death.  Cell Death Dis, 2014 May

        Electronic Technology - Eye Protection from Blue Light - Role of Lutein Mesozeaxanthin & Zeaxanthin

        Blue Light from Electronic Technology. Eye Damaging? That is the concern. Everywhere we are constantly exposed to electronic sources of blue light, including smart phones, computer displays, LED and OLED televisions and car lights. While the light emitted from a smartphone is thought to be in the visible spectrum, there is a very high amount of short wave blue light that is also emitted. LED from cars lights, especially at night, may also pose a problem for the retina. Since we are living longer and are exposed continuously to LED lights, there is real danger the retina may be irrevocably harmed.

        Natural sunlight (blue light) also causes light-induced damage to the retina, but are less intense than blue light emissions from LED devices. Therefore LED lights significantly increases the potential for toxicity to the retina. (1-4)

        • LED (light Emitting Diodes) - Due to their emitting of blue light, may damage the retina if viewed for long periods of time at close distances. White LEDs have an intense amount of blue light. Blue light is very high energy and as such can cause oxidative stress and tissue damage (including the retina). 
        • Some researchers recommend restricting internal LED lamps to "white warmth" - 2700K, which is closer to that of traditional incandescent.
        • Avoid "cool white" 5000K - 6500K. The brighter the light the more potential for harm to the retina.

           BLUE LIGHT DAMAGES RETINA

          Photoreceptors (cones and rods) in the retina provide the neuron interface to convert light to images. These photoceptors reside on the outermost parts of the retina, and are nourished and maintained by an underlying layer termed the Retinal Pigment Epithelium (RPE). Photo induced stress directly affects the health of the retina. The blue light is especially damaging, increasing oxidative stress and can lead to cellular death to either the photoreceptors or the Retinal Epithelium.

          Age-Related Macular Degeneration (AMD)  involves the progressive degradation of the photoreceptors and the  RPE. Blue light can damage and cause cellular death of these critical structures. Oxidative stress and inflammation are believed to be key factors in the development of AMD.

          NATURAL PROTECTION AGAINST DAMAGING BLUE LIGHT

          • Mesozeaxanthin. Zeaxanthin. Lutein.
            • Macular Density.
          Macula pigment density, which is composed primarily of the macular cartenoids mesozeaxanthin, lutein and zeaxanthin, is an inidicator of the capability of the macula to absorb and filter hamrful blue light. Therfore, high cartenoid density is essential for reducing damaging blue light from inflicting oxidative stress on the retina.(5) Furthermore, low macula pigment density has been in pateints with Alzheimer's Disease, indicative of possible health benefits to the brain.(6)
              • Increasing Retinal Antioxidant Factors Nrf2 and HO-1.
            Blue light photo stresses the retina by increasing the oxidative stress of the retina. Mesozeaxanthin, zeaxanthin and lutein are activators of Nrf2, a powerful cell protective factor which reduces hamrful oxidative stress in the retina, and prevents cell death. (7-9). Activation of Nrf2 leads to enhancing antioxidant protection of the retina.
               Additionally, lutein, repairs light induced damage to the retinal pigment epithelium (RPE) kayer, which is disrupted by the oxidative stress. Much like the protection of the retina cells, lutein repairs the RPE via invoking the Nrf2 endogenous antioxidant system,(10)

             

            FURTHER PROTECTION

            • Bilberry Anthocyanins. Increases Antoxidant Protection of Retina. An experimental model of retinal degeneration, produced by visible-light damage, was ameliorated by the protective antioxidant effects of bilberry anthocyanins. (11)

            • Sulforaphane. Most potent Nfr2 Activator. 
              In studies involving the Retinal Pigment Epithelium (RPE), and oxidative stress, sulforaphane was shown to  significantly up regulate antioxidant protection of the RPE by activating Nrf2 and HO-1. (12)

            • Aging Increases Damage from Blue Light in PhotoReceptor cells.              Normal protection of the photoreceptor cells and the supporting retiinal epithelium   layer, is provided by the cells inherent Nrf2 antioxidant protection against oxidative stress. However, aging is known to deplete the protective Nrf2 response, leaving the retina even more susceptible to damage by oxidative insults such as blue light. Therefore, not only does blue light inherently stress the retina and may cause cellular death, but this response is greatly amplified with retinal aging.(13-14)

               

              VISION VITALITY MAX (Mesozeaxanthin | Zeaxanthin | Lutein | Bilberry)

              XGEVITY (Glucoraphinin percursor to Sulforaphane)

               

              REFERENCES:

              (1) Coleman S. LED Lights Dangerous on Roadways and Off. 2015 Jan.

              (2) Renard G, et al. The dangers of blue light. True story. J Fr Ophtalmol.2016 May.

              (3) Jaadane I, et al.Retinal damage induced by commercial light emitting diodes (LEDs) Free Radic Biol Med. 2015 Jul.

              (4) Krigel A, et al. Light-induced retinal damage using different light sources, protocols and rat strains reveals LED phototoxicity.Neuroscience, 2016 Dec.

              (5) Lima VC, et al. Macular pigment in retinal health and disease. Int J Retina Vitreous. 2016 Aug

              (6) Nolan JM,  et al. The impact of supplemental macular carotenoids in Alzheimer's disease: a randomized clinical trial. J Alzheimers Dis. 2015

              (7) Orthan, et al. Mesozeaxanthin Protects Retina from Oxidative Stress in a Rat Model. Ocul Pharmacol Ther. 2016 Nov

              (8) Miyake S, et al. Phase II enzyme induction by a carotenoid, lutein, in a PC12D neuronal cell line. Biochem Biophys Res Commun. 2014 Apr

              (9) Zou X, et al. Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. Cell Death Dis. 2014 May

              (10) Kamoshita M, et al. Lutein acts via multiple antioxidant pathways in the photo-stressed retina. Sci Rep. 2016 Jul.

              (11) Wang Y, et al. Retinoprotective Effects of Bilberry Anthocyanins via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms in a Visible Light-Induced Retinal Degeneration Model in Pigmented Rabbits. Molecules. 2015 Dec 

              (12) Ye L, et al, Sulforaphane enhances the ability of human retinal pigment epithelial cell against oxidative stress, and its effect on gene expression profile evaluated by microarray analysis. Oxid Med Cell Longev, 2013

              (13) Sachdeva MM, et al. Nrf2 signaling is impaired in the aging RPE given an oxidative insult. Exp Eye Res. 2014 Feb;

              (14) Chen WJ, et al. Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light. Exp Eye Res. 2016 Dec