Targeted Natural Interventions
Glutathione. Since glutathione is present in very high concentrations in the lens and is essential for lens transparency, it is an important endogenous antioxidant molecule in the lens (Giblin 2000). Glutathione directly scavenges reactive oxygen species and free radicals, preventing the oxidation of structural proteins in the lens; this is particularly important in several types of cataracts, where oxidative damage to lens proteins appears to play a key role (Kamei 1993; Boscia 2000). After scavenging reactive oxygen species and free radicals, the oxidized form of glutathione is readily recycled by a specialized enzyme (Lou 2003). As we age, the recycling of glutathione decreases progressively, the pool of reduced glutathione decreases, and oxidized forms of glutathione begin to build up (Xing 2010). This is especially true in the center of the adult lens, known as the nucleus, where even small amounts of UV exposure can drive free radical formation and the generation of cataracts (Giblin 2000; Spector 1995). Nutrients currently taken by most Life Extension members, such as N-acetylcysteine, lipoic acid, melatonin, and selenium, naturally increase glutathione activity in the body (Atkuri 2007; Jariwalla 2008; Limon-Pacheco 2010; Jiang 2012).
Vitamin C. Also known as ascorbic acid, vitamin C provides extra antioxidant support in the lens by acting as a “sink” for ROS and free radicals. Its oxidized form, dehydroascorbic acid, is then converted back to ascorbic acid by glutathione and indirectly in reactions that depend on glutathione (Giblin 2000; Lou 2003; Michael 2011). Therefore, vitamin C and glutathione are thought to work together to promote proper water balance within the lens and prevent protein clumping.
The importance of vitamin C for the health of the eye is supported by the finding that vitamin C concentrations in the lens are 20-30 times higher than those in the plasma (Ravindran 2011). In addition, its importance is supported by experiments showing that inhibitors of the enzyme that recycles glutathione cause a marked increase in dehydroascorbic acid, and that dehydroascorbic acid can cause loss of transparency in the lens in animals if it is not converted back into vitamin C (Giblin 2000; Michael 2011). A study examining the effect of long-term dietary supplementation with vitamin C in women showed that supplementation over 10 years significantly decreased the incidence of early age-related cataracts at any location in the lens. Importantly, this study excluded women previously diagnosed with cataracts, to make sure that those who started vitamin C supplementation at the recommendation of their doctors, and as a result of their diagnoses, were not included (Jacques 1997). Another study, which included a large number of men and women, revealed that high consumption of vitamin C, alone or together with other antioxidants (vitamin E, beta-carotene, and zinc), protected against the development of nuclear cataracts (Tan 2009). A study that enrolled over 4000 participants reported that for every 1 mg/dL increase in vitamin C in the serum, there was a 26% decrease in cataracts (Simon 1999). Additionally, in a study in India that enrolled over 5600 individuals, a strong association was found between high serum vitamin C levels and low incidences of cataract (Ravindran 2011).
Vitamin B2. Also known as riboflavin, vitamin B2 is a vital component of flavin adenine dinucleotide (FAD). FAD, which is directly involved in breaking down carbohydrates and lipids, is important for proper cellular energy balance, and is also used by the enzyme that recycles glutathione back into its bioactive form. It was shown in several animal models that deficiency of dietary riboflavin can lead to cataracts (Bunce 1990). Several studies in humans reported that riboflavin is important in preventing the formation of cataracts. In one study, women with the highest dietary riboflavin intake, as compared to those with the lowest intake, had a lower risk for cataracts (Mares-Perlman 1995). Another study reported that individuals with the highest dietary riboflavin intake had an approximately 50% lower risk of developing cataracts (Cumming 2000).
Vitamin E. Vitamin E naturally occurs in eight different chemical forms, including alpha-tocopherol and gamma-tocopherol (Albanes 1996; MayoClinic 2012). It possesses distinct antioxidant properties and prevents the accumulation of free radicals produced during fatty acid breakdown. Since it is fat-soluble, vitamin E protects fatty tissues and cellular membranes by neutralizing free radicals and ROS. One study among women revealed that those with the highest intake of vitamin E from food and supplements had a 14% lower risk of cataracts (Christen 2008). Another study that examined participants 40–79 years old revealed lens opacities were more frequent in people with lower vitamin E levels (Leske 1995). Yet another study showed that the level of total tocopherol, which is the sum of the serum alpha-tocopherol and gamma-tocopherol, was associated with a decreased risk of developing cataracts (Lyle 1999).
Lipoic acid. Evidence suggests the potent antioxidant lipoic acid may help prevent diabetic cataract formation (Packer 1995; Maitra 1996; Kojima 2007). Since it is distributed in fat-soluble and water-soluble areas of cells and tissues, lipoic acid neutralizes a variety of free radicals (Bast 1988; Packer 1995). Lipoic acid exists in two forms: R-lipoic acid and S-lipoic acid. Of these two, R-lipoic acid in isolation was shown to prevent cataract formation (Maitra 1996). The higher efficacy of R-lipoic acid as compared to alpha-lipoic acid, which is a mixture of both forms, may be related to the higher rate of R-lipoic acid absorption by the lens.
N-acetylcysteine. N-acetyl-L-cysteine (NAC), which is a powerful antioxidant and derivative of the amino acid cysteine, has been shown to prevent opacification in the lens (Wang 2009). NAC also supports the production of glutathione (Pizzorno 1999; Zafarullah 2003; Radtke 2012). By combining NAC with diallyl disulfide, a major organosulfide found in garlic oil, researchers discovered that the latter could boost the antioxidant properties of the former, and the combination prevented the formation of cataracts (Zhao 1998). In animal models, NAC has been shown to prevent lens opacification and inhibit cataract formation (Wang 2009; Carey 2011). Another study found that the combination of NAC and glutathione ethyl ester (GSH-EE), administered as eye drops, slightly inhibited the progression of diabetic cataracts at early stages in rats (Zhang 2008).
Melatonin. Melatonin, a naturally occurring hormone, has been shown to reduce oxidative stress in the lens and protect against cataract formation (Yaqci 2006; Taysi 2008). Although the mechanism(s) involved have yet to be determined, the increased production of glutathione or direct scavenging of free radicals are thought to be involved (Abe 1994). Given that melatonin levels decline with age, and in light of the rising incidence of cataracts in the latter part of life, melatonin supplementation may be useful for cataract prevention among aging individuals (Abe 1994).
Combating Glycation Reactions and Protecting Lens Structure and Function
Carnosine. Carnosine, along with one of its derivatives N-acetyl-carnosine, is a potent inhibitor of glycation reactions and oxidative damage; it has been shown to efficiently penetrate the lens (Hipkiss 2000; Babizhayev 2012; Wang 2000). Like glutathione, carnosine levels decrease with age (Bellia 2009; Everaert 2011). At moderately high concentrations, carnosine was able to attenuate UV-induced aggregation of lens proteins (Babizhayev 2009). When delivered topically as eye drops twice daily, a solution of N-acetyl-carnosine has been shown to delay onset of diabetes-induced cataracts (Attanasio 2009; Shi 2009;).
N-acetyl-carnosine eye drops have also been shown to be effective in dogs. Visual improvements were reported in 80% of the participating dogs administered eye drops containing N-acetyl-carnosine (Williams 2006). Taken together with information from human trials and experiments in rodents, it appears that N-acetyl-carnosine eye drops may offer considerable protection against the formation and progression of cataracts (Quinn 1992; Attanasio 2009; Babizhayev 2009; Shi 2009).
Carnitine and Acetyl-L-Carnitine. Carnitine is a naturally occurring, amino acid-like compound found in all mammals with essential roles in normal function of the mitochondria, the energy powerhouses of cells; its derivative, acetyl-L-carnitine, is a powerful antioxidant and has been shown to combat glycation reactions (Reuter 2012; AMR 2010; Swamy-Mruthinti 1999). An examination of extracted human cataractous lenses showed that as opacification increased, carnitine concentrations decreased, with lenses containing the greatest opacification having about 30% lower carnitine concentrations than those with the least opacification (Gawecki 2004). In an animal model of cataracts, acetyl-L-carnitine strongly inhibited chemical-induced cataractogenesis. The researchers attributed the effects of acetyl-L-carnitine to its role as an antioxidant within the lens (Elanchezhian 2007). In a subsequent study, researchers from this same group showed that acetyl-L-carnitine also guards against “self-destruction”, or apoptosis of lens cells (Elanchezhian 2010). Evidence also indicates acetyl-L-carnitine protects against cataract development subsequent to ionizing radiation exposure by upregulating intrinsic antioxidant defense mechanisms (Kocer 2007).
Bioflavonoids. Bioflavonoids, a class of plant-derived molecules with antioxidant properties, that may be beneficial in cataracts by helping combat the accumulation of water within lens cells, which disrupts normal light refraction (Head 2001; Matsuda 2002). Specifically, the bioflavonoid quercetin, the most widely consumed flavonoid in the human diet, was shown to inhibit diabetic cataract development, possibly acting on multiple pathways, and maintain the transparency of the lens in response to oxidative stress (McLauchlan 1997; Stefek 2011). Another animal experiment showed that quercetin helped maintain lens transparency by balancing calcium, sodium, and potassium ions within the lens (Ramana 2007).
Vitamin B6. Vitamin B6, or pyridoxine, is an important water-soluble cofactor necessary for the metabolism of amino acids and the synthesis of nucleic acids required for DNA replication and repair. It has been shown to significantly reduce the production of AGEs in the diabetic lens (Jain 2002; Padival 2006). Though human studies in cataract patients still need to be conducted, a trial in which vitamin B6 and vitamin B1 were administered to diabetic patients showed the combination significantly inhibited DNA glycation in white blood cells, suggesting systemic benefit (Polizzi 2012).
Additional Support for Healthy Eyes
Carotenoids. Carotenoids, a type of pigment found in plants, absorb light and safeguard against the oxidative effects of UV rays. Several carotenoids, including lutein, zeaxanthin and meso-zeaxanthin are not only present at high levels in the retina, but also help prevent cataract formation and macular degeneration (Arnal 2009; Gao 2011; Kijlstra 2012). A study on a large group of women, ages 45–71, revealed that dietary lutein and zeaxanthin, and foods rich in these carotenoids, reduced the risk of cataracts that were sufficiently severe to require surgery (Chasan-Taber 1999). Another large study that enrolled people >40 years old found that those with a high dietary intake of lutein and zeaxanthin had a lower risk for nuclear cataracts (Vu 2006). In another study on 1802 women, subjects in the highest quintile (one-fifth) of distribution for blood levels or dietary intake of lutein and zeaxanthin were 32% less likely to have nuclear cataract compared to women in the lowest quintile (Moeller 2008). In a small double-blind, randomized clinical trial on 17 patients with cataracts, supplementation with lutein (15 mg, 3 times weekly for up to 2 years) was associated with improved visual acuity (Olmedilla 2003).
Bilberry. Bilberry is rich in anthocyanins, which are plant pigments that exert a variety of beneficial effects in the human body, including functioning as antioxidants and modulating inflammatory processes (Tsuda 2012; Karlsen 2010). Importantly, these anti-inflammatory and antioxidant effects were observed within the eye in an animal model (Miyake 2012). In an experimental model involving animals prone to age-related eye diseases such as macular degeneration and cataracts, long-term administration of bilberry extract completely abrogated impairments in the lens and retinas, whereas 70% of control animals developed cataract and macular degeneration (Fursova 2005). Bilberry has yet to be studied in large trials to assess its effects on cataracts in humans, but controlled studies have found benefits associated with bilberry supplementation, alone or in combination with other nutrients that support eye health, for eye strain and glaucoma (Kawabata 2011; Shim 2012).
Green tea and back tea. Green and black teas contain antioxidant molecules called catechins and polyphenols, which have been studied in many human health conditions (Singh 2011; Miyazawa 2000; Kerio 2013). Several animal studies show that green and/or black tea can mitigate cataract formation or progression. In one such study on rats with chemical-induced diabetes, green and black teas, administered in drinking water, were shown to retard cataract development by reducing the detrimental effects of elevated glucose on the lenses (Vinson 2005). Another study found that green tea extract bolstered antioxidant defenses and reduced the incidence of chemical-induced cataracts in an animal model (Gupta 2002). A similar study on an animal model of chemical-induced cataracts revealed that green and black tea extracts slowed progression of lens opacification (Thiagarajan 2001).
Resveratrol. Resveratrol, a natural polyphenol found in several plants (including grapes, peanuts, and pines), has multiple health benefits due to its function as an antioxidant (Zheng 2010). In an animal model of chemically-induced cataracts, resveratrol was shown to reduce oxidative stress in the lens and suppress cataract formation (Doganay 2006). Resveratrol was also able to increase the survival of human lens epithelial cell cultures that were subjected to oxidative stress, and it decreases the cellular markers of aging (Li 2011). These effects could be explained by its ability to increase the activity of intrinsic antioxidant enzymes – superoxide dismutase, catalase, and heme oxygenase (Zheng 2010).
Selenium. Selenium is a trace mineral involved in many biologic functions within the human body. Studies have shown that selenium can slow the development of cataracts by lowering oxidative stress in the lens (Zhu 2012). Although additional studies are required to determine how selenium prevents oxidative damage in the lens, it has been shown to enhance recycling of glutathione (Chada 1989; Baker 1993).