Targeted Nutritional Interventions
Anthocyanidins and Cyanidin-3-Glucoside (C3G). C3Gs are critical components of bilberry as well as being powerful antioxidants (Amorini 2001; Zafra-Stone 2007). Positive results have been noted in many animal studies and some human studies using bilberry for macular degeneration as well as other eye disorders including diabetic retinopathy, retinitis pigmentosa, glaucoma, and cataracts (Fursova 2005; Milbury 2007). C3G has been shown to improve night vision in humans by enabling the rods in the eye responsible for night vision to resume functioning faster (Nakaishi 2000). In animal cells, C3G regenerated rhodopsin (the retinal complex that absorbs light) (Amorini 2001). The anthocyanidins in bilberry decrease vascular permeability by interacting with blood vessel collagen so as to slow down enzymatic attack on the blood vessel wall. This may prevent the leakage from capillaries that is prevalent in neovascular AMD. Studies also show that bilberry increases oxidative stress defense mechanisms in the eyes (Milbury 2007). There may be additional benefits by adding vitamin E (Roberts 2007).
C3G, which is highly bioavailable, enhances other functions in the body (Miyazawa 1999; Tsuda 1999; Matsumoto 2001). Its potent antioxidant properties protect tissues against DNA damage, often the first step in cancer formation and aging of tissues (Acquaviva 2003; Riso 2005).
C3G protects endothelial cells against peroxynitrite-induced endothelial dysfunction and vascular failure (Serraino 2003). In addition, C3G fights vascular inflammation by inhibiting inducible nitric oxide synthase (iNOS) (Pergola 2006). At the same time, C3G upregulates activity of endothelial nitric oxide synthase (eNOS), which helps maintain normal vascular function (Xu 2004). These effects on blood vessels are especially important in the retina, where delicate nerve cells depend on the single ophthalmic artery for their sustenance.
In animal models, C3G prevents obesity and ameliorates blood sugar elevations (Tsuda 2003). One way it does this is by increasing gene expression of the beneficial fat-related cytokine adiponectin (Tsuda 2004). Diabetics, of course, are predisposed to severe eye problems including blindness from elevated blood sugar levels.
C3G helps induce apoptosis (programmed cell death) in a number of human cancer lines, an important step in cancer prevention (Fimognari 2004; Chen 2005). In a similar fashion (but via a different mechanism), C3G stimulates rapidly proliferating human cancer cells to differentiate so they more closely resemble normal tissue (Serafino 2004).
Finally, it was discovered that C3G is neuroprotective in experimental cellular models of brain function, helping to prevent the negative effects of the Alzheimer’s-related protein amyloid beta on brain cells (Tarozzi 2010).
Grape Seed Extract. Grape seed extract, a bioflavonoid, is a potent antioxidant. Plant-derived bioflavonoids are readily assimilated into our body when consumed. Bioflavonoids appear to protect retinal ganglion cells (Majumdar 2010). Studies conducted in fruit flies have revealed that grape seed extract attenuates the aggregation of pathologic proteins, which suggests a protective effect against macular degeneration and neurodegenerative disorders. Accordingly, fruit flies administered grape seed extract exhibited improved eye health (Pfleger 2010). Similar experiments in diabetic animals indicate that grape seed extract limits the ocular blood vessel damage seen in diabetic retinopathy (degradation of the retina), which shares some pathological characteristics with AMD (Li 2008).
Compelling laboratory evidence demonstrates that grape extracts can inhibit angiogenesis in human cells (Liu 2010). This suggests that grape seed extract may suppress the aberrant blood vessel growth observed in wet AMD.
Resveratrol. Resveratrol is a potent polyphenolic antioxidant compound produced by grapes and other plants for protection against pathogens. In humans, it exerts a broad range of physiologic effects when ingested orally. Several studies have demonstrated cardioprotective properties of resveratrol, including endothelial protection and attenuation of oxidized-LDL-induced vascular damage (Rakici 2005; Lin 2010). In addition, emerging evidence indicates that resveratrol may combat macular degeneration and promote eye health via several mechanisms. In an animal model, resveratrol was able to stave off diabetes-induced vascular lesions (Kim 2011). Moreover, this same study showed that resveratrol was able to dampen VEGF signaling in mouse retinas, a key pathologic feature of AMD. Another study corroborated these results by showing that resveratrol inhibited angiogenesis and suppressed retinal neovascularization in mice prone to develop macular degeneration due to a genetic mutation (Hua 2011). Also, several laboratory experiments have suggested additional protective mechanisms of resveratrol in macular degeneration, including protecting retinal pigment epithelial cells from hydrogen peroxide-induced oxidative stress and light damage (Kubota 2010; Pintea 2011).
Given these exciting initial findings regarding resveratrol and macular degeneration, along with its stellar track record in a variety of other conditions, Life Extension believes that individuals with AMD (especially the “wet” variety) may benefit from supplementation with resveratrol.
Ginkgo Biloba. Ginko biloba improves microcapillary circulation in the eye and slows deterioration of the macula (Thiagarajan 2002). By inhibiting platelet aggregation and regulating blood vessel elasticity, ginko biloba improves blood flow through major blood vessels and capillaries. Ginkgo is also a powerful antioxidant (Mahadevan 2008).
Glutathione and Vitamin C. Glutathione and Vitamin C are antioxidants found in high concentrations in healthy eyes and in diminished quantities in the eyes of AMD patients. Vitamin C aids glutathione synthesis in the eye. When combined with cysteine, an amino acid antioxidant, cysteine remains stable in aqueous solutions and is a precursor to glutathione synthesis. Vitamin C is important because it absorbs ultraviolet radiation, which contributes to cataracts (Tan 2008). Topical Vitamin C inhibited angiogenesis in an animal model of inflammatory neovascularization (Peyman 2007).
L-Carnosine. L-Carnosine is a naturally occurring antioxidant and anti-glycation agent. Studies have shown that carnosine inhibits lipid peroxidation and free radical-induced cellular damage (Guiotto 2005). Topically applied N-acetyl-carnosine prevented light-induced DNA strand breaks and repaired damaged DNA strands (Specht 2000), as well as improved visual acuity, glare and lens opacification in animals and humans with advanced cataracts (Williams 2006; Babizhayez 2009).
Selenium. Selenium, an essential trace mineral, is a component of the antioxidant enzyme glutathione peroxidase, important in slowing the progression of AMD and other eye disorders including cataracts and glaucoma (Head 2001; King 2008). In mice, increased expression of glutathione peroxidase protected against oxidative-induced retinal degeneration (Lu 2009).
Coenzyme Q10 (CoQ10). CoQ10 is an important antioxidant that may protect against free radical damage within the eye (Blasi 2001). Mitochondrial DNA (mtDNA) instability is an important factor in mitochondrial impairment culminating in age-related changes and pathology. In all regions of the eye, mtDNA damage is increased as a consequence of aging and age-related disease (Jarratt 2010). In one study, a combination of antioxidants including CoQ10, acetyl-L-carnitine, and omega-3 fatty acids improved the function of mitochondria in retinal pigment epithelium and subsequently stabilized visual functions in patients affected by early AMD (Feher 2005).
Riboflavin, Taurine, and Lipoic Acid. Riboflavin (B2), taurine, and R- lipoic acid are other antioxidants utilized to prevent AMD. Riboflavin is a B complex vitamin that reduces oxidized glutathione and helps prevent light sensitivity, loss of visual acuity, as well as burning and itching in the eyes (Lopez 1993). Taurine is an amino acid found in high concentrations in the retina. A taurine deficiency alters the structure and function of the retina (Hussain 2008). R- lipoic acid is considered a “universal antioxidant” because it is fat and water soluble. It also reduces choroidal neovascularization in mice (Dong 2009).
B Vitamins. Recent advances surrounding the causes of AMD have unearthed shared risk factors with cardiovascular disease (CVD) as well as similar underlying mechanisms, particularly elevated biomarkers of inflammation and CVD including C-reactive protein (CRP) and homocysteine (Vine 2005). Researchers have identified that elevated levels of homocysteine, and low levels of certain B vitamins (critical to the metabolism of homocysteine), are associated with an increased risk of AMD and vision loss in older adults (Rochtchina 2007). A strong study found that supplementing with folic acid, B6, and B12 can significantly reduce the risk of AMD in adults with cardiovascular risk factors (Christen 2009). The data, along with additional confirmatory studies, have convinced physicians to recommend B vitamin supplementation in patients with AMD. A study in more than 5000 women indicates that including folic acid (2.5 mg/day), B6 (50 mg/day) and B12 (1 mg/day) in the diet may prevent and reduce the risk of AMD (Christen 2009).
Supplement Recommendations from the Age-Related Eye Disease Study (AREDS)
The largest and most important study of nutritional supplements in AMD is the Age-Related Eye Disease Study (AREDS). The AREDS demonstrated a reduction in the risk of progression to end-stage AMD when vitamins and zinc supplementation were given to patients with advanced forms of the disease. Thousands of patients were followed for over six years. The AREDS revealed significant improvements for patients with AMD and recommended antioxidants plus zinc for most patients with AMD, except those with advanced cases in both eyes. The AREDS formula consists of the following, which is to be taken daily: Vitamin A (Beta Carotene), Vitamin C, Vitamin E, Zinc and Copper (Fahed 2010).
DHA and EPA. An 8-year trial of 2924 eligible AREDS AMD participants found that independent of AREDS supplementation, higher intakes of DHA and EPA were associated with a lower risk for progression to advanced AMD (Chiu 2009).
Zinc. Following the revealing data found from the AREDS, additional research on zinc has shown significant activity in treating AMD, specifically the dry form of the disease. In a clinical study, a zinc-monocysteine supplement significantly improved visual acuity and contrast sensitivity compared to placebo (Newsome 2008).
There has been limited success within conventional medical treatment protocols to restore lost eyesight from either form of AMD. Leading researchers are documenting the benefits of more holistic approaches to AMD. Patients are encouraged to increase physical fitness, improve nutrition (including a reduction in saturated fats), abstain from smoking, and protect their eyes from excessive light. Dietary supplementation with trace elements, carotenoids, antioxidants, and vitamins is recommended for improving overall metabolic and vascular functioning. Early screening and patient education offer the most hope for reducing the debilitating effects of the disease.