Nutrients for eye health Dr. Philip Rouchotas 2 November 2013 Nutrients for eye health - Preventing, slowing, and possibly reversing eye disease By: Philip Rouchotas, MSc, ND Bolton Naturopathic Clinic 64 King St W, Bolton, ON L7E1C7 www.boltonnaturopathic.ca firstname.lastname@example.org Jump to: Part 1 Part 2 Part 3Part 4 Part I: Degenerative Eye Disease and Antioxidants Degenerative eye disease entails gradual loss of vision due to chronic degenerative processes affecting the retina. The retina can be considered as “the back of the eyeball,” and is where the specialized cells, or photoreceptors, designed to detect light and convert light signals into nerve impulses that can be interpreted by the brain. There are many tiny blood vessels feeding the retina with oxygen and nutrients, while removing carbon dioxide and waste products. Degenerative eye disease affects the retinal cells either through local oxidative damage or by damage to the blood vessels serving the retina, leading to loss of function and ultimately, loss of vision. Two conditions account for the vast majority of degenerative eye disease: age-related macular degeneration and diabetic retinopathy. Age-related macular degeneration (AMD) is characterized by damage to the macula lutea, or “yellow spot,” which contains the fovea, the part of the retina with the highest concentration of cone-type photoreceptors and responsible for sharpest vision.(1) AMD is responsible for about 50% of cases of legal blindness, and affects about 3% of the general adult population.(1) While many factors contribute to AMD, oxidative stress is a common characteristic of these factors, including cigarette smoking, dietary habits, and excessive exposure to UV light.(1) In diabetic retinopathy, chronically elevated blood glucose levels lead to damage to the blood vessels of the eye, resulting in poor nutrient delivery, and proliferation of new blood vessels on the surface of the retina that may leak blood and fluid, blurring vision. In addition, the macula may swell causing macular edema. There is a lack of established pharmaceutical interventions for the treatment of these conditions. Currently, the best recognized agents for this condition are nutrient-based antioxidants. The Age-Related Eye Disease Study (AREDS) was a large, randomized controlled trial conducted in over 3600 patients investigating the effect of vitamin C, E, beta carotene, and zinc on the progression of AMD.(3) Over six years, supplementation with these antioxidants was able to reduce the risk of developing advanced AMD by almost 30%, with a similar reduction in the rates of moderate visual acuity loss.(3) This study is the reason why today in even conventional medical practice, these antioxidants are the primary treatment given for AMD. Our regular readers will remember the harmful effects of beta carotene, discussed at length in our June issue.(4) In brief, supplementation with vitamin A and beta carotene has been conclusively shown to cause increased risk of lung cancer in smokers, in two very large studies.(5,6) As a result of this information emerging, the second version of the AREDS study, AREDS 2, compared the original formulation containing beta carotene with a newer formulation replacing beta carotene with other non-vitamin A forming carotenoids, namely lutein and zeaxanthin, and/ or omega-3 fatty acids.(7) Over 4200 patients were enrolled. AREDS2 showed that there was not statistical difference between the old formulation or the new formulations, suggesting that replacement of beta carotene with lutein and zeaxanthin in the antioxidant formula did not decrease the effectiveness of the supplement.(7) Having covered off this first important nutritional intervention for AMD, we will cover additional agents in the remaining segments of this series. Stay tuned… References : 1. Parmeggiani F, Romano MR, Costagliola C, Semeraro F, Incorvaia C, D'Angelo S, et al. Mechanism of inflammation in age-related macular degeneration. Mediators Inflamm. 2012;2012:546786. 2. Aslam T, Delcourt C, Silva R, Holz FG, Leys A, Garcià Layana A, et al. Micronutrients in age-related macular degeneration. Ophthalmologica. 2013;229(2):75-9. 3. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119(10):1417-36. 4. Rouchotas P. Vitamin A & Beta-carotene. Naturopathic Currents. June 2013. URL: http://www.naturopathiccurrents.com/Vitamin%20A%20%26%20Beta-carotene 5. Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996;334(18):1150-5. 6. Albanes D, Heinonen OP, Taylor PR, Virtamo J, Edwards BK, Rautalahti M, et al. Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer Inst. 1996;88(21):1560-70. 7. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309(19):2005-15. Nutrients for eye health - Preventing, slowing, and possibly reversing eye disease Part II: Lutein and Xanthophylls By: Philip Rouchotas, MSc, ND Bolton Naturopathic Clinic 64 King St W, Bolton, Ontario L7E1C7 Toronto, Ontario www.boltonnaturopathic.ca In Part I we reviewed the findings of the AREDS studies, both 1 and 2. These studies found that a) antioxidants are an effective strategy for the prevention of AMD, and b) the carotenoids lutein and zeaxanthin are effective replacements for beta carotene in such a formula, so as to avoid the harmful effects of beta carotene on cancer risk. In this section, we will continue to expand on the evidence pertaining to lutein and its related compounds, called xanthophylls. Lutein and zeaxanthin bare eye-specific nutrients. Collectively, this group of substances is called the xanthophylls, simply meaning “yellow pigments”. Xanthophylls belong to the carotenoid family, however these two are not precursors to vitamin A, which is in contrast to beta carotene. As the name implies, these nutrients form macular pigments in the retina.(1) One of their functions is to quench oxidative damage that occurs in the eye secondary to routine light exposure.(1) Supplementation with lutein for instance has been shown to increase levels of macular pigment in humans.(2) The LUTEGA study followed 172 patients with AMD who were randomized to receive one of three treatments: 1) placebo, 2) a combination of lutein 10mg, zeaxanthin 1mg, docosahexaenoic acid 100mg, and eicosapentaenoic acid 30mg, or 3) double the dose as group 2. After 12 months, plasma antioxidant capacity as well as macular pigment density were both significantly increased in both treatment groups, compared to placebo.(3) Recent studies have also shown that lutein and zeaxanthin improve vision in patients with AMD. The CLEAR study administered 10mg lutein or a placebo to patients with AMD for one year.(4) At the end of the study, not only did macular pigment density increase, but supplementation with lutein prevented a decrease in visual acuity when compared to the control group after one year. In addition, among the subgroup of patients who had poor visual acuity at the beginning of the study, supplementation with lutein was able to improve visual acuity, while those patients with poor acuity receiving placebo had a worsening over the one year period.(4) We can expect more research on the effects of lutein and zeaxanthin to emerge in the next couple years. Stay tuned for Part III as we discuss the role of omega-3 fatty acids. References : 1. Loskutova E, Nolan J, Howard A, Beatty S. Macular pigment and its contribution to vision. Nutrients. 2013;5(6):1962-9. 2. Dawczynski J, Jentsch S, Schweitzer D, Hammer M, Lang GE, Strobel J. Long term effects of lutein, zeaxanthin and omega-3-LCPUFAs supplementation on optical density of macular pigment in AMD patients: the LUTEGA study. Graefes Arch Clin Exp Ophthalmol. 2013 May 22. [Epub ahead of print] 3. Arnold C, Winter L, Fröhlich K, Jentsch S, Dawczynski J, Jahreis G, et al. Macular xanthophylls and ω-3 long-chain polyunsaturated fatty acids in age-related macular degeneration: a randomized trial. JAMA Ophthalmol. 2013;131(5):564-72. 4. Murray IJ, Makridaki M, van der Veen RL, Carden D, Parry NR, Berendschot TT. Lutein supplementation over a one-year period in early AMD might have a mild beneficial effect on visual acuity: the CLEAR study. Invest Ophthalmol Vis Sci. 2013;54(3):1781-8. Nutrients for eye health - Preventing, slowing, and possibly reversing eye disease Part III: Omega-3 fatty acids By: Philip Rouchotas, MSc, ND Bolton Naturopathic Clinic 64 King St W, Bolton, Ontario L7E1C7 Toronto, Ontario www.boltonnaturopathic.ca Sections I and II have described the findings of the AREDS 1 and 2, and the LUTEGA studies. Interestingly, in these studies, the antioxidant xanthophylls lutein and zeaxanthin were co-administered with the fish-derived omega-3 fatty acids DHA (docosahexanoic acid) and EPA (eicosapentanoic acid). What we have not yet considered is the possible synergy existing between these two very different classes of nutrients! EPA and DHA are of course important nutrients in their own right. They are potent anti-inflammatory agents useful in combating most degenerative conditions including eye disease. They may be converted to neuroprotectin, which also plays a role in quenching oxidative stress in the eye.(1) These omega-3 fatty acids are also important in regulating the fluidity of retinal cell membranes, optimizing photoreceptor signaling.(1) Indeed, higher fish consumption has been shown to reduce the 12-year risk of progressing to AMD among high risk patients.(3) A very large study following almost 40,000 women over 10 years found that fish consumption of at least once per week was associated with more than 40% reduction in their risk of developing AMD, compared to those women who consumed fish less than once per month.(4) Finally, there may be another lesser known benefit of fish or fish oil supplements. It is known that high density lipoprotein (HDL), also known as “good cholesterol” is an important carrier for substances, in particular for lutein, into the eye.(5) A study by Wang et al. showed that after feeding lutein and zeaxanthin to patients with AMD, over 50% of lutein and 40% of zeaxanthin were transported by HDL, while only 22% was transported by LDL or “bad cholesterol”.(5) Fish oil supplementation has been well established as a therapy that raises HDL. One study found that supplementation with EPA among patients with depression significantly increased HDL by 0.30 mmol/L.(6) Another study found that supplementation with fish oil increased HDL among patients with metabolic syndrome and patients on cholesterol medications.(7,8) Since fish oil can increase HDL levels, presumably it may help increase delivery of lutein and zeaxanthin to the retina, thus synergizing with the effects of these eye-specific nutrients. Stay tuned for Part IV, where we discuss the role of our final agents… References : 1. Schweigert FJ, Reimann J. [Micronutrients and their relevance for the eye--function of lutein, zeaxanthin and omega-3 fatty acids]. Klin Monbl Augenheilkd. 2011;228(6):537-43. 2. SanGiovanni JP, Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res. 2005;24(1):87-138. 3. SanGiovanni JP, Agrón E, Clemons TE, Chew EY. Omega-3 long-chain polyunsaturated fatty acid intake inversely associated with 12-year progression to advanced age-related macular degeneration. Arch Ophthalmol. 2009;127(1):110-2. 4. Christen WG, Schaumberg DA, Glynn RJ, Buring JE. Dietary ω-3 fatty acid and fish intake and incident age-related macular degeneration in women. Arch Ophthalmol. 2011;129(7):921-9. 5. Wang W, Connor SL, Johnson EJ, Klein ML, Hughes S, Connor WE. Effect of dietary lutein and zeaxanthin on plasma carotenoids and their transport in lipoproteins in age-related macular degeneration. Am J Clin Nutr. 2007;85(3):762-9. 6. Mocking RJ, Assies J, Bot M, Jansen EH, Schene AH, Pouwer F. Biological effects of add-on eicosapentaenoic acid supplementation in diabetes mellitus and co-morbid depression: a randomized controlled trial. PLoS One. 2012;7(11):e49431. 7. Pedersen MH, Mølgaard C, Hellgren LI, Lauritzen L. Effects of fish oil supplementation on markers of the metabolic syndrome. J Pediatr. 2010;157(3):395-400, 400.e1. 8. Bays HE, McKenney J, Maki KC, Doyle RT, Carter RN, Stein E. Effects of prescription omega-3-acid ethyl esters on non--high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. Mayo Clin Proc. 2010;85(2):122-8. Nutrients for eye health - Preventing, slowing, and possibly reversing eye disease Part IV: Ginkgo biloba By: Philip Rouchotas, MSc, ND Bolton Naturopathic Clinic 64 King St W, Bolton, Ontario L7E1C7 Toronto, Ontario www.boltonnaturopathic.ca In previous sections we reviewed the role of antioxidants, lutein and xanthophylls, as well as omega-3 fatty acids in the treatment and prevention of AMD. In this last section we consider an important herb in this area: Ginkgo biloba. Gingko improves microcirculation to the retina, and improving tissue oxygenation and clearance of potentially damaging substances and mediators. Four studies have evaluated the use of ginkgo in the treatment of degenerative eye disease. Fies et al. examined the effectiveness of Ginkgo in age-related macular degeneration.(1) A total of 99 patients with impaired vision due to AMD were given either high dose (240mg) or low dose (60mg) of Ginkgo for six months. After four weeks, there was already ‘marked improvement of the study participants' vision,” with more pronounced improvements in the high dose group. The tolerability of Ginkgo was good, suggesting few side effects. Lebuisson et al. conducted a smaller randomized controlled trial among patients with AMD, assessing effects of Ginkgo on the visual appearance of the retina upon eye examination, as well as on visual acuity. This study found that there was a significant improvement in long distance visual acuity following treatment with Ginkgo.(2) With respect to diabetic retinopathy, a Polish study examined the preventative effects of Ginkgo supplementation among children with long-standing type I diabetes.(3) Investigators gave Ginkgo for three months and then reassessed the children for any anatomical or functional changes in their eye health. Following Ginkgo treatment, the children had better color vision test results: 25% of children had shown pathological results before treatment, compared to only 4% following Ginkgo treatment. Finally, a French study also assessed the effects of Ginkgo on diabetic retinopathy.(4) A total of 29 adults with early stage diabetic retinopathy were randomized to treatment with Ginkgo or placebo for six months. After this time, there was a worsening in patients who were in the placebo group, but there was a trend for improvement in visual function among patients treated with Ginkgo. These studies suggest a potentially important role for Ginkgo in the treatment of eye disease, in addition to the nutrient based therapies discussed in preceding sections. Because Ginkgo may act as a “blood thinner,” it should not be given to patients with blood clotting disorders, hemorrhagic conditions, or on anticoagulation therapy. References : 1. 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. 2. Lebuisson DA, Leroy L, Rigal G. [Treatment of senile macular degeneration with Ginkgo biloba extract. A preliminary double-blind drug vs. placebo study]. Presse Med. 1986;15(31):1556-8. 3. Bernardczyk-Meller J, Siwiec-Prościńska J, Stankiewicz W, Fichna P, Pecold K, Korman E. [Influence of Eqb 761 on the function of the retina in children and adolescent with long lasting diabetes mellitus--preliminary report]. Klin Oczna. 2004;106(4-5):569-71. 4. Lanthony P, Cosson JP. [The course of color vision in early diabetic retinopathy treated with Ginkgo biloba extract. A preliminary double-blind versus placebo study]. J Fr Ophtalmol. 1988;11(10):671-4.