vitamins

Supplements for AMD

A look at the specific supplements that can slow age-related macular degeneration, how they work and patient candidacy.

Steven M. Newman, O.D., C.N.S.,
Plantation, Fla.

The room was dark, calm and peaceful. What I did see was cast in shadow by a small tapered candle placed in a far corner away from the padded massage table I lay upon. Soft, chanting music seemed to come from all four walls, but I could see no speakers. I was on my back, doing my best to practice deep breathing techniques that help me through stressful times. (It's not easy to meditate, as someone is slowly, meticulously placing surgical sharp pins between your toes.)

It was during this acupuncture session — my third — when something incredible happened: I began to smell vanilla emanating from the candle. This was incredible for me because a near-fatal bicycle accident took my ability to smell several months prior. My neurologist explained I was lucky to have my other four senses after fracturing three bones in my skull and recovering from a subdermal hematoma.

The fact that acupuncture made a difference where allopathic medicine couldn't reaffirmed to me that the body really does work as a whole. This is particularly true with age-related macular degeneration (AMD), as research has shown that vitamin and mineral supplementation can slow the disease and even reverse its signs and symptoms.¹

Here, I discuss the specific supplements designated for AMD, how they work and patient candidacy.

Supplements

A combination of antioxidants and zinc were shown to reduce advanced AMD risk by 25% in patients with extensive intermediate drusen, large drusen or noncentral geographic atrophy (GA) in one or both eyes, or those with advanced AMD or visual acuity <20/32 attributable to AMD in one eye, according to the Age-Related Eye Disease Study (AREDS).¹ (AREDS defined advanced AMD as photocoagulation or other treatment for choroidal neovascularization or photographic documentation of GA involving the macula's center, non-drusenoid retinal pigment epithelial detachment, serous or hemorrhagic retinal detachment, hemorrhage under the retina or the retinal pigment epithelium and/or subretinal fibrosis.) The AREDS study also revealed that those with moderate-to-advanced AMD who took a combination of antioxidants and zinc reduced their risk of moderate vision loss (a loss in visual acuity score of at least 15 letters) by 19%.¹

This combination of antioxidants and zinc: A total of 500 milligrams of vitamin C, 400 International Units of vitamin E, 15 milligrams of beta-carotene (often labeled as equivalent to 25,000 International Units of vitamin A), 80 milligrams of zinc as zinc oxide and two milligrams of copper as cupric oxide. (Copper was added to prevent copper deficiency anemia, which is linked with high levels of zinc ingestion.)¹

So how, specifically, do these antioxidants and zinc work to slow AMD progression? One study on patients who used the AREDS formula suggests antioxidants decrease oxidative stress-induced endothelial dysfunction, possibly by eliminating reactive oxygen species.² Oxidative stress can be thought of as a chain of charged particles causing damage to the cell. The more stress, the longer and stronger the chain. Vitamin C slows the progression of AMD by neutralizing the charge, directly and indirectly, yielding the charged particles harmless.³ Vitamin E in high concentrations may improve one's chance of prolonging lens health and improving macular health with advancing age.⁴ Meanwhile, beta-carotene has been shown necessary for night vision, wound healing and proper functioning of the immune system.⁵ Zinc, which is present in high concentrations in the eye, is thought to slow AMD possibly by preventing cellular damage to the retina.⁶ Retinal zinc content has been shown to abate with age, and the activity of some zinc-dependent retinal enzymes has also been shown to lessen with age.

In addition to the aforementioned findings, four other discoveries emerged from AREDS. First, during the study period itself, two studies were released that showed cigarette smokers who took beta-carotene were at increased risk for lung cancer and mortality. Second, subjects in the zinc-only arm showed an excess of self-reported anemia and a frequency of genitourinary hospitalizations (e.g., unspecified urinary tract infection and prostatic hyperplasia in men and stress incontinence in women).¹ Third, high levels of dietary omega-3 long-chain polyunsaturated fatty acid (LCPUFA) intake of eicosapentaenoic acid (EPA) was found associated with a decreased risk of progression from bilateral drusen to central GA in neovascular AMD patients.⁷ Finally, high dietary intake of lutein/zeaxanthin was found independently linked with a reduced likelihood of neovascular AMD, GA and large or extensive intermediate drusen.⁸

Based on these discoveries, AREDS 2 was born. Its objectives:⁹

► Study the effects of high supplemental doses of the dietary xanthophylls (lutein and zeaxanthin) and Omega-3 LCPUFA (DHA and EPA) on the development of advanced AMD.
► Study the effects of these supplements on cataract and moderate vision loss (doubling of the visual angle or the loss of 15 or more letters on the Early Treatment Diabetic Retinopathy Study [ETDRS] chart).
► Study the effects of eliminating beta-carotene in the original AREDS formulation on the development and progression of AMD.
► Study the effects of reducing zinc in the original AREDS formulation on the development and progression of AMD
► Validate the fundus photographic AMD scale developed from the Age-Related Eye Disease Study.

AREDS 2 enrollment concluded in June 2008, with participants ages 50 to 85 to be followed between five and six years. The estimated completion date: December 2012.

So, how, specifically, have lutein, zeaxanthin and Omega-3 LCPUFAs been shown to work to slow AMD progression? Lutein and zeaxanthin are specific carotenoids thought to protect the macula from degenerating by filtering out blue light at the prereceptoral level of the retina or by reducing DNA damage to the photoreceptor cells.^10,11 Omega-3 LCPUFAs possess anti-inflammatory effects and, when converted into neuroprotectin, have been shown to protect against oxidative-induced apoptosis in the retina. Also, they are responsible for the fluidity and supply to the photoreceptor membrane.¹² (Omega 3's tend to balance lipids in our bloodstream, and lipid molecules are responsible for transporting carotenoids to the retina.)

Patient candidacy

The AREDS authors concluded that patients who have intermediate AMD in one or both eyes and patients who have advanced AMD in one eye, but not the fellow eye and without contraindications, should be considered AREDS formula candidates.¹ The contraindications: increased risk of lung cancer in smokers (beta carotene), heart failure in those with vascular disease or diabetes (vitamin E) and hospitalizations for genitourinary conditions (zinc).¹³ Also, patients undergoing treatment for chronic conditions, such as cancer and diabetes, should not begin the AREDS regimen without first discussing it with their healthcare team, due to the medications they are already taking and possible interactions.¹⁴

Should you decide to prescribe the AREDS formula, be sure to warn the patient of potential adverse events, such as kidney stones (Vitamin C), fatigue, muscle weakness, decreased thyroid gland function, increased hemorrhagic stroke risk (vitamin E) yellowing of the skin (beta carotene), anemia and decreased high-density lipoprotein cholesterol and upset stomach (zinc).¹ In addition, educate the patient that the data from AREDS suggests the combination therapy provides a treatment benefit for AMD and visual acuity outcomes through seven years in patients at risk for advanced AMD progression.

Although the AREDS2 results won't be released for another year, research already does exist regarding patient candidacy for lutein, zeaxanthin and Omega-3 LCPUFA supplements. To start, the Lutein Antioxidant Supplementation Trial (LAST) II revealed that those who had the lowest macular pigment optical density (MPOD) and, were therefore, likely in the most need of supplementation, were also the most likely to benefit from either lutein alone or in combination with an antioxidant.¹⁵ Keep in mind that most retinal disease experts now believe that if the patient's MPOD can be increased, the risk of degeneration decreases. (To determine a patient's MPOD, heterochromic flicker photometry devices are available.)

The LAST II study's purpose: to determine whether specific dietary interventions increased MPOD and visual function in patients who had atrophic AMD. The prospective, 12-month randomized, double-masked, placebo-controlled trial was comprised of 90 atrophic AMD patients assigned randomly to either 10mg lutein; 10mg lutein with vitamins, minerals and antioxidants; or maltodextrin placebo and were seen for one year.¹⁵

Yet the LUtein Nutrition effects measured by Autofluorescence (LUNA) study suggests that even with the proper flow of antioxidants to the eye, a limit may exist to the amount of carotenoids certain retina's absorb.¹⁶ The possible reason for this: The liver is responsible for producing lipoproteins, which transport lutein and zeaxanthin to the eye. Consider our current American society, where the average 55-year-old uses three different prescription medications. The liver must process these drugs, and some of the popular medications, such as statins used to lower cholesterol, are even toxic to this vital organ. Now, keep in mind that some of these same individuals may have caused some liver damage with a varying degree of alcohol consumption throughout the years, and it makes sense that some patients experience greater benefits from lutein and zeaxanthin supplementation than others. In fact, the study's authors suggest a correlation between lipid profiles and AMD, though do not expand upon it. In addition, for centuries, traditional Chinese medicine (TCM) has successfully treated macular degeneration as an imbalance of the liver.¹⁷ According to TCM, the healthier the liver, the less risk of AMD.

The purpose of the LUNA study: to investigate, in terms of MPOD and serum concentrations of its constituent carotenoids, the response to supplemental lutein and zeaxanthin and co-antioxidants. The study was comprised of 108 AMD subjects with a mean age of 71.5 and a control group of 28 subjects. The AMD group received a daily supplement of 12mg lutein and 1mg zeaxanthin, both provided as ester 120mg vitamin C, 17.6mg vitamin E, 10mg zinc, 40 microg selenium for six months. The control group received no dietary supplementation or modification. The results: A statistically significant increase in MPOD in the supplement group vs. the control group. Supplementation with 12mg lutein and 1mg zeaxanthin, combined with co-antioxidants, resulted in an increase of MPOD at 0.5° eccentricity in a majority of subjects.¹⁶

Another study reveals that spouses who consumed the same amount of lutein and zeaxanthin had similar carotenoid serum levels, but a varying MPOD change as a result.¹⁸ This makes sense, as the liver's many processes required for perfect balance to produce the transporting lipoprotein are also unique to all individuals, regardless of lifestyle. Another finding: Body Mass Index was inversely proportional to MPOD.

Very few people are not good candidates for Omega 3's. If, however, the patient has certain allergies to fish or has dietary restrictions (vegan/kosher), plantbased (flax seed, etc.) omega 3's work fine.

The whole body concept

Just as acupuncture between my toes opened channels in my olfactory system, certain vitamins and minerals along with a healthy lifestyle (exercise and diet — keep that liver healthy!) can benefit the retina. As a result, consider offering the aforementioned vitamins and minerals to those you feel could benefit from them. OM

1. Age-Related Eye Disease Study Research Group. A randomized, placebocontrolled, 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 Oct;119(10):1417-36.
2. Pemp B, Polska E, Karl K, et al. Effects of antioxidants (AREDS medication) on ocular blood flow and endothelial function in an endotoxin-induced model of oxidative stress in humans. Invest Ophthalmol Vis Sci. 2010 Jan;51(1): 2-6.
3. Beatty S, Koh H, Phil M, et al. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2000 Sep-Oct;45(2): 115-34.
4. EyeScience. Macular Health Formula. Eye Vitamin Comparison Chart. http://eyescience.com/products/macularhealth-formula (Accessed 11/11/11')
5. All About Vision. Guide to Choosing Nutritional Supplements for Vision. www.allaboutvision.com/nutrition/supplements.htm. (Accessed 11/11/11')
6. Office of Dietary Supplements: National Institutes of Health. Dietary Supplement Fact Sheet: Zinc. http://ods.od.nih.gov/factsheets/Zinc-QuickFacts (Accessed 11/11/11')
7. SanGiovanni JP, Chew EY, Agron E, et al. The relationship of dietary omega-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS report no.23 Arch Ophthalmol. 2008 Sep;126 (9):1274-9.)
8. SanGiovanni JP, Chew EY, Agron E, et al. The relationship of dietary carotenoid and vitamin A, E and C intake with age-related macular degeneration in a case-control study: AREDS report no. 22 Arch Ophthalmol. 2007 Sep;125(9): 1225-32.)
9. Age-Related Eye Disease Study 2: The Lutein/Zeaxanthin and Omega-3 Supplement Trail. About AREDS2. www.areds2.org. (Accessed 11/11/11')
10. Loane E, Nolan JM, O'Donovan, et al. Transport and retinal capture of lutein and zeaxanthin with reference to age-related macular degeneration. Surv Ophthalmol. 2008 Jan-Feb;53(1):68-81.
11. Sasaki M, Yuki K, Kurihara T, et al. Biological role of lutein in the light-induced retinal degeneration. J Nutr Biochem. 2011 Jun 8.
12. Schweigert FJ, Reimann J. Micronutrients and their relevance for the eye — function of lutein, zeaxanthin and omega-3 fatty acids. Klin Monbl Augenheilkd. 2011 Jun;228(6): 537-43.
13. Evans J. Antioxidant supplements to prevent or slow down the progression of AMD: a systematic review and metaanalysis. Eye (Lond.) Jun;22(6):751-60.
14. Age-Related Eye Disease Study — Results. The Age-Related Eye Disease Study (AREDS) is a major clinical trial sponsored by the National Eye Institute, one of the Federal government's National Institutes of Health. Frequently Asked Questions. www.nei.nih.gov/amd. (Accessed 11/10/11')
15. Richer S, Devenport J, Lang JC. LAST II: Differential temporal responses of macular pigment optical density in patients with atrophic age-related macular degeneration to dietary supplementation with xanthophylls. Optometry. 2007 May;78(5):213-9.
16. Trieschmann M, Beatty S, Nolan JM, et al. Changes in macular pigment optical density and serum concentrations of its constituent carotenoids following supplemental lutein and zeaxanthin: the Luna Study. Exp Eye Res. 2007 Apr; 84(4):718-28.)
17. No authors listed. New England Journal of Traditional Chinese Medicine, Winter2004 (3): 1-3.
18. Wenzel AJ, Sheehan JP, Burke JD, et al. Dietary intake and serum concentrations of lutein and zeaxanthin, but not macular pigment optical density, are related in spouses. Nutrition Research 2007;27:462-469.)

Dr. Newman is in private practice in Plantation, Fla., where he specializes in ocular disease and nutritional/holistic optometry. In addition, he has written and lectured extensively on nutrition and the eye and is an advisory board member for the ocular nutrition society (www.ocularnutritionsociety.org). Finally, his book Feel More Alive Now, is available at amazon.com. E-mail him at drstevennewman@yahoo.com, or send comments to optometricmanagement@gmail.com.