Life Extension Magazine May 2006
Nutritional Strategies for Preventing Age-Related Vision Loss
By Edward Rosick, DO, MPH, MS
Antioxidant Supplements for Eye Health
Because high C-reactive protein levels appear to be associated with risk for ARMD and numerous other age-related diseases, health-conscious adults are advised to implement strategies to lower CRP. One way to do this is through beneficial antioxidants. Multiple published studies demonstrate the efficacy of various antioxidant supplements in reducing CRP values.
One recent study examined the effect of alpha tocopherol (vitamin E) on C-reactive protein levels in 25 healthy volunteers and 47 people with type II diabetes. In this five-month study, the use of vitamin E supplements markedly decreased CRP levels in both healthy volunteers and those with diabetes.5
Another study examined the relationship between C-reactive protein levels and concentrations of various vitamins and minerals among 14,519 men and women. Higher CRP levels were significantly related to diminished concentrations of antioxidants, including vitamin C, beta-carotene, lutein, zeaxanthin, and selenium. According to the study authors, “these results suggest that the inflammatory process [reflected by high CRP levels], through the production of reactive oxygen species, may deplete stores of antioxidants.”6
With the knowledge that ARMD is at least partly connected to an inflammatory cascade reflected in high CRP levels, and that antioxidants effectively counter high CRP levels, it makes sense to investigate whether antioxidants help protect against ARMD. A study recently published in JAMA examined this very possibility.
In their report entitled “Dietary Intake of Antioxidants and the Risk of Age-Related Macular Degeneration,” researchers in the Netherlands conducted a population-based cohort study of 4,170 men and women, with an average age of 68. The scientists determined the subjects’ average antioxidant intake and incidence of ARMD using dietary questionnaires and detailed eye exams. Over a mean follow-up period of eight years, 560 participants developed macular degeneration. However, those with a high intake of foods rich in beta-carotene, vitamins C and E, and zinc had a 35% lower risk of developing ARMD.
The study authors noted, “recent data suggest that oxidative protein modifications may play a crucial role in the formation of drusen. This implies that antioxidants may have their strongest effect at the initiation of the disease.” They believe that antioxidants like vitamins A, C, and E may work synergistically in warding off ARMD. According to the research team, “We therefore conclude that dietary antioxidants may delay the development of early [ARMD], and possibly, of [ARMD] in general.”7
Protective Effects of Lutein and Zeaxanthin
Emerging research confirms that lutein and zeaxanthin can help protect vision by guarding against both cataracts and ARMD. These safe, beneficial compounds are chemically classified as carotenoids, the naturally occurring pigments found in many colorful fruits and vegetables.
Interestingly enough, lutein and zeaxanthin are the only carotenoids generally found in the eye. While high levels of other carotenoids are found in the blood and plasma—beta-carotene and lycopene are two examples—hardly any zeaxanthin is found in plasma. In the eye, lutein and zeaxanthin are found in both the lens and macula. The two help give the macula its striking, deep yellow hue. While researchers continue to study the precise roles played by lutein and zeaxanthin in the eyes, there is general agreement that both carotenoids protect the eye in two important ways.
First, lutein and zeaxanthin absorb near-to-UV blue light, which has the highest energy and is therefore the wavelength most potentially damaging to the retina and macula. Second, lutein and zeaxanthin are potent antioxidants that quash the formation of free radicals.8 By generating damage in both the lens and macula, free radicals may contribute to both cataracts and ARMD.
A solid body of scientific evidence points to the great potential of lutein and zeaxanthin in combating cataracts and ARMD. In three studies conducted in the late 1990s, men and women with a high intake of lutein and zeaxanthin had significantly lower risks of developing cataracts compared to those with a low intake of these carotenoids.1,9,10
A more recent randomized, double-blind, placebo-controlled study showed that lutein supplements can help improve vision in people with existing cataracts.11 Seventeen men and women with cataracts, aged 55-73, were given lutein (15 mg), vitamin E in the form of alpha tocopherol (100 mg), or placebo three times a week for up to two years. Subjects who took the alpha tocopherol supplements experienced a stabilization of their vision, while those taking placebo saw a decline in vision. Subjects who took lutein showed a significant increase in their visual acuity and glare sensitivity. According to the study authors, “a higher intake of lutein, through lutein-rich fruit and vegetables or supplements, may have beneficial effects on the visual performance of people with age-related cataracts.”
Another study published in JAMA evaluated the relationship between carotenoids—including lutein, zeaxanthin, and other antioxidants—and the risk of developing ARMD.12 In this case-control study, 356 ARMD patients, aged 55-80, were compared to 520 control subjects. The results unequivocally demonstrated that a higher dietary intake of carotenoids is associated with a significantly lower risk of developing ARMD. Specifically, those who had the highest intake of carotenoids had a 43% reduction in ARMD risk. Not surprisingly, the study authors stated that “among the specific carotenoids, lutein and zeaxanthin . . . were the most strongly associated with a reduced risk for [ARMD].”
Ginkgo Biloba May Improve Vision
Ancient Chinese medical manu-scripts indicate that for at least 5,000 years, the leaves of the ginkgo tree have been used for various health conditions, including supporting circulation, cognition, and respiratory function. Numerous studies indicate that ginkgo biloba may help fight dementia and Alzheimer’s disease.13-16
Exciting new findings suggest that ginkgo may also hold promise in countering ARMD. German researchers recently conducted a controlled, double-blind study of human subjects suffering from the dry form of ARMD. The subjects were given 60 or 240 mg/day of ginkgo over a six-month period. At the study’s end, the subjects who used either dose of ginkgo showed marked improvement in their vision. However, those taking the higher dose saw the most improvement. The study authors concluded that “the results demonstrate the therapeutic efficacy of [ginkgo extract] in patients with senile, dry macular degeneration, with obvious benefits in everyday life.”17
Carnosine Counters Oxidation and Glycation
Advanced glycation end products, or AGEs, are molecules that may be just as important as free radicals in many of the pathological processes associated with aging, including the development of cataracts. AGEs adversely affect the physical and biochemical properties of proteins and the tissues in which they are present, such as the eye lens. Fortunately, carnosine not only protects against the ravages of oxidative damage, but also inhibits the formation of advanced glycation end products.
Carnosine is a natural, safe compound comprising the amino acids beta-alanine and L-histidine. Numerous studies have shown that carnosine inhibits lipid peroxidation and free radical-induced cellular damage.18-21 In addition, carnosine has demonstrated anti-aging effects in laboratory animals.20 Carnosine may elicit these effects due to its ability to inhibit AGE formation and protein cross-linking.18-21
Multiple studies suggest that eye drops containing carnosine may help in the prevention and management of cataracts. In one 24-month, placebo-controlled study, an acetylated type of carnosine—N-acetylcarnosine—was used in eye-drop form in 49 patients with cataracts.22 Cataract patients who received carnosine eye drops twice daily demonstrated significantly im-proved vision compared to those receiving placebo eye drops. In addition, topographical studies of the patients’ eyes revealed that people using the carnosine eye drops had fewer areas of lens clouding from cataract formation. The eye drops were well tolerated, and there were no reports of adverse ocular or systemic side effects. The researchers concluded, “topical [carnosine] shows potential for the treatment and prevention of cataracts.”
High Homocysteine Tied to ARMD Risk
While some mainstream medical doctors may be surprised to learn that there is a link between free radicals, elevated C-reactive protein levels, and ARMD, they may be even more surprised to know that new studies link high homocysteine levels to macular degeneration.
Homocysteine is an amino acid produced in the body through the breakdown of methionine, an amino acid that occurs in many foods, including meats, fish, and eggs. Studies have associated high levels of homocysteine with elevated risk for a number of diseases, including atherosclerosis and stroke. A new study published in the American Journal of Ophthalmology has shown that high homocysteine levels may increase risk for ARMD.
In this case-controlled, cross-sectional study, researchers examined fasting plasma homocysteine levels in 934 men and women, 547 of whom had intermediate or advanced ARMD and 347 of whom served as healthy control subjects.23 Median plasma levels of homocysteine were significantly higher in subjects who had advanced ARMD; high homocysteine was also significantly associated with a higher risk of developing ARMD. Regarding a possible mechanism by which homocysteine might contribute to the development of ARMD, the authors stated that “high homocysteine levels may cause oxidative injury to endothelial cells, enhance peroxidation of low-density lipoprotein, and alter blood-clotting mechanisms . . . because homocysteine levels can be modified by dietary means or nutritional supplements, additional studies to clarify the role of homocysteine in the development or progression of [ARMD] are warranted.”
Folic Acid, B12 Help Lower Homocysteine
Additional studies are needed to more precisely ascertain homocysteine’s role in ARMD. In the meantime, however, it would be wise to take steps to reduce high homocysteine levels and thus possibly avoid the consequences of ARMD. In numerous studies, two safe and inexpensive nutrients—folic acid and vitamin B12—have been highly effective in lowering potentially lethal homocysteine levels.
In a study conducted in 2004, researchers examined the effects of a daily dose of 5000 mcg of folic acid and 250 mcg of vitamin B12 on the homocysteine levels of patients with significant coronary artery disease, defined as having at least 70% blockage of a major coronary artery.24 After only 12 weeks, patients taking folic acid and vitamin B12 supplements reduced their homocysteine levels by 32%.
In a similar study conducted in China the same year, 152 patients with high homocysteine levels were given 5 mg of folic acid daily over an eight-week period.25 As in the earlier studies, homocysteine levels dropped markedly, in this case by 34%.
Studies that are even more recent confirm the homocysteine-lowering effects of folic acid and vitamin B12. In a meta-analysis published in the American Journal of Clinical Nutrition, researchers analyzed 25 randomized, controlled trials examining the effects of folic acid and B12 supplements on homocysteine levels in a total of 2,596 patients.26 The results showed that at dosages of 200 mcg, 400 mcg, 800 mcg, 2000 mcg, and 5000 mcg/day, folic acid decreased homocysteine levels by 13%, 20%, 23%, 23%, and 25%, respectively. Vitamin B12 supplements at a dose of 400 mcg/day produced an additional 7% reduction in homocysteine.
Begin Protecting Your Vision Now
The wonderful gift of sight is something most of us take for granted until it is somehow altered or diminished. By eating a diet abundant in fruits and vegetables, avoiding smoking, wearing ultraviolet radiation-blocking sunglasses when outdoors, maintaining healthy C-reactive protein and homocysteine levels, and using nutritional supplements with proven benefits for eye health—including antioxidants such as vitamins A, C, and E, carotenoids like lutein and zeaxanthin, and ginkgo biloba, carnosine, folic acid, and vitamin B12—you can help ensure healthy vision that lasts a lifetime.
1. Lyle BJ, Mares-Perlman JA, Klein BE, Klein R, Greger JL. Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study. Am J Epidemiol. 1999 May 1;149(9):801-9.
2. Hankinson SE, Stampfer MJ, Seddon JM, et al. Nutrient intake and cataract extraction in women: a prospective study. BMJ. 1992 Aug 8;305(6849):335-9.
3. Vine AK, Stader J, Branham K, Musch DC, Swaroop A. Biomarkers of cardiovascular disease as risk factors for age-related macular degeneration. Ophthalmology. 2005 Dec;112(12):2076-80.
4. Seddon JM, Gensler G, Milton RC, Klein ML, Rifai N. Association between C-reactive protein and age-related macular degeneration. JAMA. 2004 Feb 11;291(6):704-10.
5. Devaraj S, Jialal I. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Radic Biol Med. 2000 Oct 15;29(8):790-2.
6. Ford ES, Liu S, Mannino DM, Giles WH, Smith SJ. C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among United States adults. Eur J Clin Nutr. 2003 Sep;57(9):1157-63.
7. van LR, Boekhoorn S, Vingerling JR, et al. Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA. 2005 Dec 28;294(24):3101-7.
8. Krinsky NI, Johnson EJ. Carotenoid actions and their relation to health and disease. Mol Aspects Med. 2005 Dec;26(6):459-516.
9. Brown L, Rimm EB, Seddon JM, et al. A prospective study of carotenoid intake and risk of cataract extraction in US men. Am J Clin Nutr. 1999 Oct;70(4):517-24.
10. Chasan-Taber L, Willett WC, Seddon JM, et al. 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.
11. Olmedilla B, Granado F, Blanco I, Vaquero M. Lutein, but not alpha-tocopherol, supplementation improves visual function in patients with age-related cataracts: a 2-y double-blind, placebo-controlled pilot study. Nutrition. 2003 Jan;19(1):21-4.
12. Seddon JM, Ajani UA, Sperduto RD, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA. 1994 Nov 9;272(18):1413-20.
13. Bridi R, Crossetti FP, Steffen VM, Henriques AT. The antioxidant activity of standardized extract of Ginkgo biloba (EGb 761) in rats. Phytother Res. 2001 Aug;15(5):449-51.
14. Youdim KA, Joseph JA. A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Radic Biol Med. 2001 Mar 15;30(6):583-94.
15. Kanowski S, Herrmann WM, Stephan K, Wierich W, Horr R. Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry. 1996 Mar;29(2):47-56.
16. Le Bars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA. 1997 Oct 22;278(16):1327-32.
17. Fies P, Dienel A. Ginkgo extract in impaired vision—treatment with special extract EGb 761 of impaired vision due to dry senile macular degeneration. Wien Med Wochenschr. 2002;152(15-16):423-6.
18. Guiotto A, Calderan A, Ruzza P, Borin G. Carnosine and carnosine-related antioxidants: a review. Curr Med Chem. 2005;12(20):2293-315.
19. Hipkiss AR, Michaelis J, Syrris P. Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross-linking agent. FEBS Lett. 1995 Aug 28;371(1):81-5.
20. Hipkiss AR. Carnosine, a protective, anti-ageing peptide? Int J Biochem Cell Biol. 1998 Aug;30(8):863-8.
21. Gallant S, Semyonova M, Yuneva M. Carnosine as a potential anti-senescence drug. Biochemistry (Mosc.). 2000 Jul;65(7):866-8.
22. Babizhayev MA, Deyev AI, Yermakova VN, et al. Efficacy of N-acetylcarnosine in the treatment of cataracts. Drugs RD. 2002;3(2):87-103.
23. Seddon JM, Gensler G, Klein ML, Milton RC. Evaluation of plasma homocysteine and risk of age-related macular degeneration. Am J Ophthalmol. 2006 Jan;141(1):201-3.
24. Lee BJ, Huang MC, Chung LJ, et al. Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease. Eur J Clin Nutr. 2004 Mar;58(3):481-7.
25. Guo H, Lee JD, Ueda T, et al. Hyperhomocysteinaemia & folic acid supplementation in patients with high risk of coronary artery disease. Indian J Med Res. 2004 Jan;119(1):33-7.
26. Anon. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr. 2005 Oct;82(4):806-12.
27. Smeeth L, Hubbard R, Fletcher AE. Cataract and the use of statins: a case-control study. QJM. 2003 May;96(5):337-43.
28. Available at: http://www.merck.com/product/usa/pi_circulars/m/mevacor/mevacor_pi.pdf. Accessed February 27, 2006.
29. Available at: http://www.zocor.com/zocor/ shared/documents/english/pi.pdf. Accessed February 27, 2006.
30. Mori M, Li G, Abe I, et al. Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat. J Clin Invest. 2006 Feb;116(2):395-404.