Macular degeneration supplement Saffron 2020; a natural solution for macular health

Introduction:

Good nutrition is very important for general health and more specifically for eye health. Good nutrition helps our body to grow, repair the wear and tear caused by the aging process, and to function properly.

In various studies and clinical trials, antioxidant vitamins and phytochemicals found in certain foods have been linked with better eye health. They help to maintain healthy cells and tissues in the eye.

Natural nutrients for reducing the risks of age-related macular degeneration:

Lutein & Zeaxanthin, the macular pigments

It is known that the retina needs key anti-oxidants – lutein and zeaxanthin, and also vitamins A, B2, C and E, and zinc – to protect itself from daily oxidative damage. Anti-oxidants are substances that may protect the cells against the effects of free radicals, the molecules produced when the body breaks down food or fights infection, or when exposed to environmental stressors like air pollution, tobacco smoke and radiation. Once they are produced they can damage other cells. They are believed to play a part both in the natural aging process and in age-related vision loss.

Two large clinical trials, called the ‘Age-Related Eye Disease Study’ (AREDS) showed that antioxidant vitamins C, E, and the minerals zinc as zinc oxide, and copper as cupric oxide, can help to slow down the progression of age-related macular degeneration (AMD).

Following the two AREDS clinical trials, there have been over 150 smaller scale studies looking at how vitamins and minerals, both from food and in a vitamin supplement can help eye health in general, and in particular AMD and cataracts. A number of recent studies have looked specifically at saffron, resveratrol, lutein and zeaxanthin, which have been associated with healthy eyes and protection against damage to retina. Studies have shown how these ingredients can modulate the function of retinal genes, stimulate repair mechanism, protect against oxidative and inflammatory damage and help preserve eyesight.

Saffron 2020, patented saffron supplement for age-related macular degeneration:

One particular study looked at effect of saffron on modulating expression level of retinal genes and non-coding RNA sequences (ncRNA). In this study, pre-treatment of with saffron showed that saffron interacts very significantly with gene expression to protect and repair photoreceptors via various mechanisms, including reduction of inflammation, supporting cell membrane integrity, and having regulatory effect on tissue oxidative protection mechanism. Further studies are needed to unravel details of mechanism of neuroprotective action of saffron in retinal cells (Natoli et al., 2010).

Research has shown that many people do not get enough vitamins, minerals and important eye nutrients from their diet, and therefore some people might consider taking a supplement for their general health and for eye health.

Use of nutritional supplements has given a hope for development of new natural remedies for ameliorating age-associated loss of eyesight and against eye diseases such as AMD and cataracts, and for decelerating disease progression as a function of adult age.

Age-related macular degeneration (AMD)

Age-related macular degeneration (AMD) is a leading cause of adult vision loss in developed countries and accounts for more than 50% of blindness in the United States, and the number of individuals affected is expected to double in 2020. (Huang et al. 2008; National Eye Institute. Vision problems in the US 2006).

It is estimated that there are over 20 million cases of AMD in the US and Europe, and up to 17 million elderly have at least early signs of AMD called Age Related Maculopathy (ARM) [ww.nei.nih.gov/eyedata]).

The worldwide incidence of the disease increases from one in ten people over the age of 60 to more than 1 in 4 people over the age of 75. According to AMD Alliance, macular degeneration is more common than Parkinson’s disease, Alzheimer’s disease, breast cancer and prostate cancer combined. The resulting visual impairment from AMD disease affects patient’s quality of life, and the individual’s emotional and social health, as well as independence is adversely affected.

AMD causes high economic burden to the society and health care system because inflicted patients with impaired vision have an increased risk of fall, fracture, and depression and need daily support services or nursing home care.

AMD is becoming a major public health concern because the population is aging and as a direct result an increase in incidence is awaited.

Although vision loss is becoming a major public health problem, current therapy options for AMD, specially for the dry form of AMD are limited, and therefore, preventive interventions specially novel nutritional supplements are needed for reducing this increasing burden on society. Nutritional supplements have particular role in managing AMD and cataracts (Huang et al. 2008).

Pathology of age-related macular degeneration or AMD:

Vision loss in patients with AMD is attributable to photoreceptor death in central retina. Growing scientific evidence suggests a role for retinal pigment epithelial (RPE) cell damage and death caused by oxidative stress. The early stage of pathogenesis is associated with degeneration of retinal pigment epithelial (RPE) cells, which are responsible for degradation of photoreceptor outer segments that have been shed. RPE death leads to photoreceptor death (Sheu et al. 2010). The retina is particularly susceptible to oxidative damage because of its high consumption of oxygen, the transparency of the cornea, aqueous humour and lens that allow continuous exposure of retina to light creating an intrinsic vulnerability of the retina to damage via oxidative stress.

Risk factors affecting development of AMD include age greater than 50, Caucasian race, nutrition, smoking, atherosclerotic vascular disease, genetics, and sunlight exposure (Sheu et al. 2010; Thornton et al. 2005). Age-related macular degeneration occurs in response to prolonged exposure of the eye to visible and ultraviolet light, as well as photooxidative damage or chemical stresses from a glucose- and oxygen-rich blood supply to the retina of the eye. Over time, these factors all contribute to the breakdown of our retinal light-sensing cells, particulalry those in the centre of retina or macula.  As degeneration of retinal cells in the macula progresses, patients lose their central and fine vision and become less able to see what they are trying to focus on. Consequently, the ability to read, drive, do fine work, recognize faces or read newspaper and perform many other daily tasks can become impaired, even before the onset of legal blindness, that comes with late stage development of AMD when there is widespread  destruction and degeneration. It is important to protect the structural integrity and function of the macula of the eye early  in order to prevent it from degeneration and progression to more advanced stages.

Age-related macular degeneration (AMD or also known as ARMD) & role of nutrition in preserving eye health and protecting against AMD:

Several epidemiological studies have suggested a link between low consumption of carotenoids and antioxidant vitamins and minerals with increased risk of development and progression of AMD and cataracts (Kubota et al. 2009; Chucair et al. 2007; Bartlett & Eperjesi, 2003(B); Evans, 2006).  The risk of develping  macular degeneration is reduced in those ingesting higher amounts of certain natural plant carotenoids. These carotenoids also delay early-stage macular degeneration from worsening.

The use of nutritional supplements for improving health, protecting eysight and delaying age-related chronic diseases has become a common practice and standard of care (Maraini et al. 2009; Joseph et al. 2009; and Jones 2007).

Antioxidant micronutrients such as, zinc and copper facilitate activity of antioxidant enzymes such as catalase and peroxidase in the body. Zinc also acts as a prosthetic group for the antioxidant enzyme superoxide dismutase, which will be unable to function in the absence of the prosthetic group. Similarly, other nutrients such as vitamin E, vitamin C and lutein and zeaxanthin have also shown to possess biological antioxidative properties protecting retinal cells against photoxidative damage (Bartlett & Eperjesi, 2004).

Role of special nutrients and plant extracts in eye health:

Saffron for eye health in age-related macular degeneration (AMD) and cataracts:

Patients with age-related macular degeneration benefited from eye health properties of saffron.

Saffron (Crocus sativus) is a spice containing the antioxidant carotenoids crocin and crocetin. Saffron has been known for its antioxidant, anti-inflammatory, and cell protective effects. Daily doses of up to 1.5 g are thought to be safe (Schmidt et al. 2007). Crocin, which is the main carotenoid in saffron has a stronger antioxidant activity than α-tocopherol and can prevent the formation of peroxidized lipids and partly restore superoxide dismutase (SOD) activity (Ochiai et al. 2004).

A recent review on biological properties of saffron (Bathaie, & Mousavi, 2010) has indicated a wide range of useful biological properties in neuronal, cardiovascular, atherosclerosis, respiratory system, and blood pressure, and ocular benefits.

The most important result for eye health benefits of saffron came from a recent double blind, placebo-controlled, cross-over clinical study. Results indicated that taking oral supplementation of saffron at 20 mg/day for three months induced a short-term and significant improvement of retinal function in early AMD. In this study cone-mediated ERG in response to high-frequency flicker (focal ERG, FERG) was employed as the main outcome variable. The effects, however, disappeared when patients stopped taking the saffron pills. No adverse side effects were reported in this study.  According to Professor Silvia Bisti from the University of Sydney, who carried out the research, ‘Patients’ vision improved after taking the saffron pill’ (Falsini et al. 2010). The above scientific studies demonstrat saffron’s ability to improve visual acuity and to improve sensitivity of the retina to light in people with macular degeneration.

In a 15-month follow up clinical study, the same researchers observed that patients continued to get the benefits of the supplement for as long as they took the saffron capsules. This study confirmed initial findings that saffron may hold the key for tackling vision loss in AMD.

According to this recent study taking long term saffron supplement led to: “improvement in contrast and colour perception, reading ability, and vision at low luminances, all ultimately leading to a substantial improvement in the patients’ quality of life.”.  This new study showed that taking saffron supplementation for long term presents a safe natural solution to help prevent eyesight loss in old age, and as reported “no adverse systemic side effects were recorded” (Piccardi et al. 2012).

Degeneration of the macula (the central part of the retina where the rods and cones are most dense) leads to loss of central vision in people over 60. Saffron protects and prevents the steady breakdown of light-sensitive cells in the center of the retina, the macula, which is the root cause of age-related macular degeneration. Saffron improves light sensitivity in people affected with macular degeneration. Light sensitivity is a major manifestation of the disease.  Daily Supplementation with 20mg high quality saffron improved the light-sensing abilities of retinal cells in early age-related macular degeneration. This is an unprecedented results and has created a hope for treatment of macular degeneration with natural compounds, at low cost and literally no side effects.

The first report on eye health benefits of saffron and its main active compound, crocin, came from Xuan et al. (1999) that suggested crocin analogs can be used to treat ischemic retinopathy and/or age-related macular degeneration. The suggestion was based on the observation that intraperitoneal injection of crocin analogs (10 mg/Kg) significantly increased the blood flow in the retina and choroid.

The carotenoid crocin has protective effect against blue light- and white light-induced rod and cone death in bovine and primate retinal cell cultures. In the presence of 80 micromolar crocin complete protection of photoreceptors was achieved against the damaging effect of light exposure (Laabich et al. 2006). Light exposure leads to photoreceptor degeneration, and several epidemiologic studies have suggested that long-term history of exposure to light may have some impact on the incidence of age-related macular degeneration. In humans environmental lighting conditions have a deleterious effect on the progression of AMD and retinitis pigmentosa (Thomas et al. 2007; Taylor et al. 1992).

Safranal is another active compound in saffron that has shown retinal protective effects, and is considered to be contributing to the eye health properties of saffron. The P23H mutation of the rhodopsin-encoding gene (RHO) is the most prevalent cause of retinitis pigmentosa (RP), anther eye disease that causes degeneration of retina and loss of vision. In one study administration of safranal to homozygous P23H line-3 rats, preserved both photoreceptor morphology and number. In this study, safranal slowed photoreceptor cell degeneration and ameliorated the loss of retinal function and vascular network disruption in P23H rats. Electroretinographic recordings showed higher a- and b-wave amplitudes under both photopic and scotopic conditions.

The capillary network in safranal-treated P23H rats was also preserved. According to this study: ” .…Safranal could be potentially useful to retard retinal degeneration in patients with retinitis pigmentosa…” (Fernández-Sánchez et al. 2012).

Saffron has shown retinal neuroprotective properties in animal models of retinal degenerative disorders. Saffron exhibited protective effect against light-induced damage of photoreceptors, by maintaining both morphology and function. Saffron-treated animals exhibited both the preservation of the photoreceptor layer and reduction of photoreceptor death, when exposed to bright continuous light (Maccarone et al 2008).

Saffron for its regulatory mechanism on cellular targets (Natoli et al, 2010) and for possessing diverse biological properties beneficial to AMD, is a superior ingredient for an ideal ocular nutritional supplement. Crocetin, the aglycon form of the carotenoid crocin, significantly inhibited photoreceptor degeneration and retinal dysfunction in in vitro and in vivo tests. In one experiment crocetin protected against retinal damage by inhibiting an increase in caspase-3 and -9 activities after retinal damage by tunicamycin or hydrogen peroxide (Yamauchi et al. 2010).

In a study, crocetin (carotenoid from saffron) inhibited VEGF-induced retinal angiogenesis. Abnormal angiogenesis can lead to wet AMD, in whihc blood vessels disruptively invade the retina and cause rapid vision loss. Vascular endothelial growth factor (VEGF) plays important role in angiogenesis. Crocetin was tested on human umbilical vein endothelial cells (HUVECs) and human retinal microvascular endothelial cells (HRMECs). A number of positive effects were observed in this study: 1) Crocetin inhibited VEGF-induced tube formation in HUVECs co-cultured with human fibroblast; 2) Suppressed the VEGF-induced HRMEC migration (as a mechanism of inhibition of tube formation); 3) Inhibited VEGF-induced increase in p38 level (one mechanism for inhibition of migration); 4) Prevented VEGF-induced decrease in VE-cadherin in HUVECs and/or HRMECs. According ot the authors of this paper: “…Crocetin would be expected to pass thorough the blood-retinal barrier in mice, rats, and humans following oral administration, and therefore may be effective in suppressing angiogenesis in the retina.” (Umigai et al. 2012).

In another study Crocetin prevented ischemia-induced retinal damage through the inhibition of oxidative stress (Ishizuka et al, 2013).

Effect of saffron on amyloid beta-peptide: Amyloid beta is a constituent of drusen in dry AMD. Amyloid beta is an activator of the complement system, and together are implicated in the pathogenesis of AMD. Saffron is shown to inhibit Aβ amyloid formation and disrupt amyloid aggregates (Ghahghaei et al, 2013).

Based on the recent research saffron activates mechanisms of self-defence and self-repair in the retina of the eye protecting it against oxidative damage. Saffron can restore some of the lost vision, and then can stabilize retina against further degeneration, which is the classic cause of development and progression of AMD.

According to ‘recent research: “…the golden culinary herb [saffron] can both protect and reverse the course of sight degeneration…..The herb saffron may hold one of the keys to preventing the loss of sight in old age – and may even help to improve vision…..”.

According to a recent study (Marki et al, 2013) saffron prevented selenite-induced cataract formation in Wistar rats, possibly through the reinforcement of antioxidant status, reduction of the intensity of lipid peroxidation, protection of the sulfhydryl groups, and inhibition of proteolysis of the lens. These findings highlight the anticataractogenic potential of saffron by virtue of its antioxidant property.

The mechanisms by which saffron exerts its neuroprotective action on retinal cells are different and include:

– Modification of gene expression levels working on repair pathways and protective mechanisms

– Antioxidant.

– Anti-inflammatory.

– Inhibiting TNF-α induced apoptosis, by modulating Bcl-2 family protein expression.

– Suppressing caspase activation.

– Antiapoptic, leading to preservation of the photoreceptor morphology and function.

– Anti-neovascularization (anti- VEGF), preventing pathologic angiogenesis in wet-AMD.

Resveratrol for eye health, and for age-related macular degeneration (AMD):

Current search suggest that resveratrol supplementation could offer the potential for modulating the risks in development and progression of AMD and cataracts.

Results from a recent study suggested: “… the potential use of resveratrol as a therapeutic agent to prevent light-induced retinal degeneration” (Kubota et al. 2010; Kubota et al. 2009).

Resveratrol has a diverse range of potential beneficial effects in our body. During the last decade we have seen a growing interest in the effects of resveratrol on the eye, both for disease prevention and treatment.

Resveratrol is the main biologically active polyphenol in red wine, and is also found in red grapes, peanut, Japanese giant knotweed, blueberries, bilberries, and cranberries.

Resveratrol has shown vascular enhancing properties, and it has been suggested to be effective in the microcirculation of the eye, to help prevent or treat ocular diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma.

More specifically, resveratrol has shown promising anti-oxidant, antiapoptotic, anti-tumourogenic, anti-inflammatory, antiangiogenic and vasorelaxant properties.

Impaired blood flow and subsequent ischaemic changes are implicated in the pathology of several ocular diseases including age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma, which are common causes of sight loss.

Therefore, resveratrol for it vascular enhancing effects has the potential to prevent the onset and progression of a wide range of ocular diseases via a diverse range of molecular mechanisms.

Anti-oxidant compounds such as resveratrol are able to combine with damaging free radicals, thereby stabilising them and preventing sustained oxidation.

Oxidative stress is thought to be involved in progression of several eye diseases including primary open-angle glaucoma (POAG), a major cause of worldwide irreversible blindness.

Oxidative stress caused cell damage, leading to increased apoptotic cell death. Treatment with resveratrol has shown therapeutic potential in primary open-angle glaucoma (POAG). Resveratrol inhibited the increased production of intracellular reactive oxygen species (iROS), which in turn prevented the induction of the pro-inflammatory markers such as interleukin-1a (IL1a), interleukin-6 (IL-6). Resveratrol also prevented the expression of the cellular senescence marker sa-β-galactosidase (sa-β-gal), which is typically induced by oxidative stress.

Similarly the formation of age-related cataracts is also associated with prolonged oxidative stress, in which oxidation of proteins within the lens is thought to play a crucial role in the pathogenesis of cataracts.

When tested in rat against selenite-induced cataract formation, resveratrol caused an increase in the levels of reduced glutathione (GSH) in rat lenses and erythrocytes. High levels of GSH protect the lens against oxidative damage. GSH levels have been shown to decline in age-related human cataracts and selenite-induced cataracts in rats, suggesting an essential role in preserving lens function. Therefore, resveratrol is suggested for its potential role in preventing development or progression of age-related cataracts in human.

Resveratrol has also shown significant antidiabetic effects, and has been shown to have therapeutic potential for protecting against or preventing diabetic retinopathy (DR). Diabetic retinopathy (DR) is a common problem in both type of diabetes and is a leading cause of acquired blindness. It is believed that hyperglycemia leads to an imbalance between production of reactive oxygen species (ROS) and neutralization of ROS by antioxidants, contributing to the pathogenesis of diabetic retinopathy (DR). Furthermore, treatment with resevratrol has shown beneficial effects in protecting against vessel leakage, pericyte loss, and VEGF protein levels (Nagineni et al, 2014).

In a study resveratrol used on prophylaxis basis showed neuroprotective effect on experimental retinal ischemic injury. Resveratrol reduced the ischemia-mediated thinning of the whole retina and in particular the inner retinal layers. Based on the results authors suggested that: “…resveratrol may have therapeutic value for the management of retinal ischemic disorders” (Vin et al, 2013).

Resveratrol preserves neurons (including photoreceptors) and has been reported to prevent Aβ-induced retinal degeneration via various mechanism of action including:
– Anti-inflammatory effects against amyloid-β (Aβ) peptides-triggered microglial activation, via a mechanism involving the TLR4/NF-κB/STAT signaling cascade. J Neurochem. 2012 Feb;120(3):461-72. doi: 10.1111/j.1471-4159.2011.07594.

– Inhibited inflammatory responses via the mammalian target of rapamycin (mTOR) signaling pathway. PLoS One. 2012;7(2):e32195. doi: 10.1371/journal.pone.0032195.

– Inhibited Aβ-induced RPE barrier disruption and expression of IL-6, IL-8, and MMP-9. and Inhibited Aβ-mediated NF-kB activation and decrease of the NF-kB inhibitor, IkBa. Braz J Med Biol Res. 2013 Aug;46(8):659-69. doi: 10.1590/1414-431X20132903.

– By activation of SIRT1 (by resveratrol), an NAD+-dependent deacetylase, prevented retinal ganglion cell (RGC) loss in optic neuritis.

– Reseveratrol as a SIRT1 activator prevent cell loss by reducing oxidative stress and promoting mitochondrial function in neuronal cell line.

Therefore, it is suggested that: “.. Resveratrol has the potential to preserve neurons [prevent neuronal loss] in other neurodegenerative diseases.” (Khan et al, 2012).

In another study resveratrol has shown strong protective effects against oxysterol-induced cell death and VEGF secretion. Because drusen lesions contain numerous types of lipid including esterified and unesterified cholesterol, the pathogenesis of AMD might have some similarities with atherosclerosis. The pro-oxidative environmental conditions of eye favour the spontaneous cholesterol oxidation into oxysterols in RPE cells triggering cytotoxic, pro-inflammatory,pro-oxidative, and pro-angiogenic activities responsible for AMD lesions. Oxysterols can induce VEGF secretion on human retinal cells, implying a pro-angiogenic effects. Resveratrol has been described to down-regulate VEGF synthesis, and when used at 1 mM prevented neovascularization, which is a major complication of AMD. The authors suggested: “.. a new therapeutic perspective” for treatment of AMD by using resveratrol(Dugas et al. 2010).

Resveratrol in both in vitro and in vivo experiments (in mouse retinas) inhibited pathological angiogenesis, induced by laser injury,by a sirtuin-independent pathway. Resveratrol inhibited the proliferation and migration of vascular endothelialcells. Abnormal angiogenesis is central to the pathophysiology of AMD. Treatment of mice with resveratrol at 45 mg/kg, delivered through subcutaneous osmotic pump, exhibited a significant protective role for resveratrol against the development and/or sustenance of CNV. In this study resveratrol inhibited the migration and proliferation of endothelial cells in sprouting vasculature and induces cell cycle arrest.

According to Dr. Rajendrar S. Apte the senior investigator of this study, “resveratrol could potentially be a preventive therapy in high-risk patients. And because it worked on existing, abnormal blood vessels in the animals, it may be a therapy that can be started after angiogenesis has already started to cause its damage.” The authors further indicated that: “… resveratrol is suggested for treating ocular diseases with exuberant and abnormal angiogenesis including age-related macular degeneration (AMD), diabetic retinopathy, and retinopathy of prematurity.”   (Khan et al, 2010).

In a recent clinical study resveratrol oral pill was tested in patients that refused intra-vitreal anti-VEGF injections or failed to respond to Lucentis®, Avastin® or Eylea. Results showed that oral resveratrol caused restoration of retinal structure and visual function with dramatic short-term anti-VEGF type effect including anatomic restoration of retinal structure with improvement in choroidal blood flow. The visual function improvements after oral supplementation with resveratrol is very significant finding and merits further investigation. The effect effect of resveratrol was bilateral with the added benefit of better RPE (retinal cell) function. Results from this study suggests: “… resveratrol as an adjunct therapy to improve retinal pigment epithelial cell (RPE) function (Richer et al, 2013).

Another study showed that resveratrol is effective and efficient in suppressing endothelial cell proliferation and migration, and in fact at a dose of 10 μM exhibited an effect comparable to that of bevacizumab (Avastin), on HUVEC proliferation and migration. Authors of this study suggested that: “.…given the small molecular mass of resveratol and its free diffusion inside cells, further exploration is warranted to test the use of resveratrol in treating pathologic angiogenesis in vivo , e.g., to inhibit neovascularization in macular diseases such as age-related macular degeneration (AMD)”  (Cao et al, 2010).

Resveratrol has also shown protective effects in retina via modulation of nitric oxide synthase in in vitro and in vivo oxygen-induced retinopathy models (Kim & Suh 2010).

Resveratrol due to its antiapoptotic and antioxidative properties was able to reverse significantly the loss of cell viability in ARPE-19 cell cultures. This suggested a broad beneficial effect by resveratrol against retinal diseases associated with the loss of RPE cells such as AMD (Mansoor et al, 2010, PMID: 19959636). As previously mentioned, oxidative damage to RPE cells is suggested as an underlying cause of retinal damage in AMD and  resveratrol has shown potent antioxidant effect and inhibition of apoptosis on human RPE cells. “….Resveratrol inhibited caspase pathways and also reactive oxygen/nitrogen species (ROS/RNS) formation, which ultimately protected the cell viability of ARPE-19 cells. The authors suggested that resveratrol could be beneficial to a number of diseases such as cataracts, neurodegeneration, and age-related macular degeneration (AMD). Therefore, further studies with resveratrol are needed for developing prophylaxis or therapy for the treatment of retinal diseases in humans.” (Mansoor et al 2010).

In a study results showed that resveratrol protects against ER stress and degeneration in the retina. It inhibits tunicamycin-induced vascular degeneration and ER stress markers. The authors suggested that: “… resveratrol could be a potential drug candidate for vascular dysfunction in the retina.”(Li et al, 2012).

It is also known that light damage to the retina accelerates retinal degeneration, and that resveratrol can prevent retinal degeneration associated with damage by light (Kubota et al. 2010).

In a recent single study on an 80-year-old man with complaints of unremitting night driving difficulty and parafoveal deposition of retinal lipofuscin, visible clearing of RPE lipofuscin was observed by using 100 mg resveratrol for 5 months. Clinically measurable and subjective improvements in vision, including self-reported night vision, dramatic improvement in contrast sensitivity function and mental function was also achieved (Richer et al. 2009).

The antioxidative, gene modifying and anti-angiogenic properties of resveratrol together with preclinical and clinical evidence, provided a strong rationale for using it in Saffron 2020.

Saffron 2020 for eye health in age-related macular degeneration (AMD) and cataracts:

Lutein and Zeaxanthin

Lutein and zeaxanthin are macular carotenoids of dietary origin. Lutein is the main pigment in macula of the ye and together with its isomer zeaxanthin are also known as macular pigments or zanthophylls. There is large body of scientific evidence on eye health properties of the macular pigments (Christen et al. 2008; Fletcher et al. 2008; Johnson et al. 2008; Moeller et al. 2008; Alves-Rodrigues and Shao 2004; Richer et al. 2004; Olmedilla et al. 2003; Brown et al. 1999).

Lutein is a naturally occurring pigment found in dark green leafy vegetables such as spinach, kale and collard greens. Lutein in the eye is thought to act as an antioxidant and photoprotectant. Lutein plays an important protecting role in our eyes by acting as a kind of natural sun block protecting the retina against damaging effects of too much light. Because free radicals may play a role in macular degeneration, the effect of lutein is also attributable to its antioxidant effect (Nolan et al. 2009; Johnsonet al. 2008; Chucair et al. 2007; Rotstein et al. 2003; Landrum et al 1997).

It is well established that dietary intake of lutein/zeaxanthin is inversely associated with development of neovascular AMD, geographic atrophy, and large or extensive intermediate drusen (Sangiovani et al 2007; Huang et al. 2008). Experiments have shown that regular consumption of lutein supplements can increase the macular pigment density in the eye, which may potentially reduce the risk for later development of AMD (Landrum et al. 1997).

Supplementation with lutein is associated with increased macular pigment optical density (MPOD). Lutein helped stabilize visual acuity, and increased vision related quality of life in patients with AMD. No evidence of harmful side effect was found in any of these studies. (Richer et al 2007; Trieschmann et al 2007; Sartore et al. 2006). In one particular study patients ingesting lutein supplement experienced significant improvements in several objective measurements of visual function including glare recovery, contrast sensitivity, and visual acuity versus placebo. Patients experienced a 50% increase in macular pigment density relative to those on placebo pills (Richer et al. 2004).

Supplements containing lutein and zeaxanthin have promoted photoreceptor survival and differentiation in cell culture by exerting neuroprotective and antiapoptotic effect on retinal photoreceptors, which may be through the antioxidant properties of the pigments or by activation of intracellular signaling pathways. These in vitro findings support the epidemiological evidence that dietary supplements may act as factors that modulate processes implicated in AMD pathogenesis and progression (Chucair et al. 2007). In fact supplementation with lutein and zeaxanthin has led to improvements in visual function in patients with age-related macular disease (Bartlett & Eperjesie, 2005; Bartlett & Eperjesi, 2004).

Lutein may also be useful for treatment of retinitis pigmentosa, an inherited form of eye disease that causes progressive vision loss (Bahrami et al. 2006).

Despite the eye health benefits of xanthophylls, recent data suggest that dietary intake levels of these two pigments declined in Europe and the US. The average American ingests about one to two mg of lutein daily (Bartlet & Eperjesi, 2006), supporting the evidence for eye health benefits by supplementation.

An average dietary intake of greater than 6 mg/day of lutein is not uncommon, however, because lutein competes with other carotenoids for absorption it appears to be sensible to put a maximum limit of 6 mg/day lutein in a dietary supplement (Jones 2007).

The ocular health benefits of supplementation with antioxidant vitamins, zinc and carotenoids lutein/zeaxanthin are studied in patients from well-nourished developed countries, and one would expect that their beneficial effects on eye would be greater in other populations with different, likely to be less rich, dietary patterns and nutrient intake (Dherani et al.2008).

Vitamin A:

Vitamin A is a well characterised and recognized lipid soluble nutrient, which helps maintain normal vision and mucous membranes. Retinal is the active form of vitamin A in the body that is involved in photochemical reactions in the retina and is needed for normal vision, particularly for night vision, which can be affected over the years and specially in AMD. European Food Safety Authority (EFSA) Journal 2010; 8(10): 1754.

Vitamin B2:

Vitamin B2, also known as riboflavin, is a water soluble vitamin that is involved in a wide variety of metabolic pathways, including the biosynthesis and catabolism of amino acids, fatty acids and carbohydrates. Riboflavin has an important role as a coenzyme in energy-yielding metabolism, and contributes to normal metabolism of iron. Riboflavin has antioxidant properties involved in protecting cellular components from oxidative damage. Riboflavin deficiency can cause opacity of the lens, burning and itching of the eyes, photophobia, and a loss of visual acuity. Riboflavin is a coenzyme that can help maintain normal vision. European Food Safety Authority (EFSA) Journal 2010; 8(10): 1814.

Vitamin C:

There have been many reports on eye health benefits of vitamin C and vitamin E in combination with zinc. Vitamin C is a water soluble antioxidant vitamin that helps protect DNA, proteins and lipids, also in retinal cells, from the oxidative damage caused by free radicals. Additionally, vitamin C contributes to normal energy-yielding metabolism and helps maintain physical health. European Food Safety Authority (EFSA) Journal 2010; 8(10): 1815.

Vitamin E:

Vitamin E is a potent biological antioxidant that is thought to have functional importance in maintaining cellular membrane integrity. Vitamin E has central role in protection against free-radical induced cellular damage. Vitamin E protects poly-unsaturated fatty acids of cells by scavenging free radicals. Dietary intake of vitamin E is known to protect DNA, protein and lipids from oxidative damage. Free radical damage has been implicated in a number of degenerative and age-related diseases including AMD and cataracts. European Food Safety Authority (EFSA) Journal 2010; 8(10): 1816.

Zinc:

There is established relationship between the dietary intake of zinc and normal DNA synthesis and cell division, protection of DNA, proteins and lipids from oxidative damage. Zinc is involved in maintenance of normal vitamin A metabolism, and maintenance of normal vision. “In retina and retinal pigment epithelium, there is evidence that zinc can modify photoreceptor plasma membranes, regulate the light-rhodopsin reaction, modulate synaptic transmission and serve as an antioxidant”. European Food Safety Authority (EFSA) Journal 2010; 8(10): 1819, and EFSA Journal, 2009: 7(9) 1229.

Zinc is a cofactor for the potent antioxidant enzyme superoxide dismutase, which helps to protect cellular components from oxidative damage by neutralising free radicals. Zinc is an antioxidant micronutrients and a cofactor involved in activity of more than 200 enzymes such as alcohol dehydrogenase, DNA polymerase and RNA polymerase (Bartlett & Eperjesi, 2004).

Copper:

Dietary intake of copper contributes to protection of DNA, proteins and lipids from oxidative damage, and contributes to normal energy-yielding metabolism, iron transport, maintenance of the normal functional of the nervous system and immune system. European Food Safety Authority (EFSA) Journal 2010; 7(9): 1211, and European Food Safety Authority (EFSA) Journal 2010; 9(4): 2079

 You can nutritionally support your eye health for the long haul!

Cataracts:

Experiments have shown that free radicals mediate the formation of cataract. The major causes for cataract formation are free radicals, which are neutralized by the presence of endogenous antioxidants in the eye. Among the natural antioxidants and carotenoids vitamin C, vitamin E and lutein are well known for their anti-cataract properties.  And similarly as it was discussed with the role of antioxidant and development and progression of AMD, antioxidants can be supplemented in the diet for a better protection against free radicals and oxidative damage.  Vitamin C and vitamin E are capable of preventing lipid peroxidation, thereby preventing formation of excess free radical. It is particularly important that the combination of antioxidant vitamins such as vitamins C and E appear to have a synergistic effect on cataract prevention. In summary, there is significant inverse trends with risk of cataract and dietary intake of lutein/zeaxanthin and antioxidant vitamins.

There is a growing body of observational evidence to suggest a possible beneficial effect for lutein/zeaxanthin in delaying cataract formation and maintaining lens clarity (Christen et al. 2008; Moeller et al. 2008; Brown et al. 1999; Chasan-Taber et al. 1999)

Saffron 2020, premium natural health product for eye health:

Saffron 2020 is designed to address the above concerns for protecting retina and lens of the eye by taking advantage of the health benefits of saffron, resveratrol, lutein and other nutrients. Saffron 2020 is more particularly formulated for individuals affected by AMD or cataracts.

Saffron 2020 takes advantage of positive effects from a synergistic combination of saffron and resveratrol for providing both anti-oxidant, anti-inflammatory and gene modulation effects, and for influencing macular function in AMD and lens clarity in cataracts. The beneficial effects are enhanced by including well-documented eye health nutrients; vitamins A, B2, C and E, zinc, copper, lutein and zeaxanthin in combination with saffron and resveratrol.

Saffron 2020 has been evaluated by Health Canada and the NPN license was granted in 2012 (NPN 80030166).

Health Canada has granted the following health claims for Saffron 2020:

1. Helps to maintain eyesight in cataracts and age-related macular degeneration (AMD).

2. Helps to support eye health in cataracts and age-related

macular degeneration (AMD).

3. Helps to reduce the risk of developing cataracts.

4. Helps to improve macular pigment optical density.

5. Antioxidants for the maintenance of eye health.

6. Helps to maintain eyesight.

7. Antioxidants for the maintenance of good health.

Saffron 2020 helps maintain healthy vision and good eye health, and is recommended to individuals if they:

● Are a healthy adult and want to maintain eye health over the years

● Are diagnosed with age-related macular degeneration (AMD) or cataracts and want to maintain eyesight
● Have family history of AMD or cataracts and want to protect eye health
● Have lifestyle risk factors such as smoking
● Have diet lacking important eye health nutrients at the required level
● Are exposed to high levels of light from the sun or computer screens or experience eye strain

Saffron 2020 can improve quality of life for many millions of members of our aging society, and can lead to significant savings to the healthcare system.

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