<h2>Practice points</h2><ul><li>The Macular Disease Foundation recommend patients diagnosed with age-related macular degeneration (AMD), in consultation with a healthcare professional, should consider taking a daily dose of:18 <ul><li>Zinc 80 mg</li><li>Vitamin C 500 mg</li><li>Lutein 10 mg</li><li>Copper 2 mg</li><li>Vitamin E 400 IU</li><li>Zeaxanthin 2 mg</li></ul> </li><li>Antioxidants lutein and zeaxanthin may reduce the risk of developing AMD16</li><li>Encourage monitoring changes in vision should be reported immediately to an eye specialist</li><li>Daily use of an Amsler grid plus regular check ups should be recommended1</li></ul><h2>Description</h2><ul><li>A group of degenerative diseases of the retina that cause progressive, painless loss of central vision1</li><li>Affects one in seven people over the age of 50 in Australia and is the most common cause of legal blindness1</li><li>Oxidative damage to the retina may be involved in the pathogenesis of AMD11</li><li>2 forms: dry AMD – results in gradual vision loss; wet AMD – results in sudden vision loss. The dry form can develop into wet AMD1</li><li>There is no cure, however research indicates that diet and lifestyle changes, including the use of an appropriate nutritional supplementation may slow down the progression of the disease1 </li></ul>

<h2>Management guidelines</h2><ul><li>Slow progression of the disease through diet and lifestyle changes and supplementation where appropriate</li><li>Monitor condition with regular check ups</li></ul>

Management

<h2>Primary recommendations</h2><h2>ZINC AND ANTIOXIDANTS1</h2>Mechanism of action<ul><li>Antioxidants such as vitamin E and C are found in high concentrations in the eye.14</li><li>Zinc is also found in high concentration in the eye and functions in various antioxidant enzymes and compounds. There can be an age-related decline in zinc levels in the eye which may increase vulnerability to free radical damage14</li></ul>ResearchThe Age-Related Eye Disease Study (AREDS) is one of the only studies for which there is good, long-term evidence for the benefits of high dose nutrients for people diagnosed with dry AMD.1 AREDS investigated the effect of zinc and antioxidant nutrients on AMD progression and loss of visual acuity in high risk patients over 5 years.11<ul><li>There was a 25% risk reduction for progression to advanced AMD in patients with intermediate stage AMD in both eyes, or late stage AMD in one eye</li><li>There was a 19% risk reduction of at least moderate visual acuity loss in patients at high risk of developing advanced AMD. The decreased risk was considered a result of the decreased risk of progression to advanced AMD</li><li>There was no benefit in patients with no signs of AMD</li><li>10 year follow up – the zinc group had reduction in all-cause mortality (HR 0.83)12</li></ul>Dosage<ul><li>Vitamin E: 400 IU/day18 </li><li>Vitamin C: 500 mg/day18 </li><li>Zinc: 80 mg/day1</li><li> Adverse effects <ul><li>Vitamin E: generally well tolerated. Doses below 1500 IU daily are very unlikely to result in haemorrhage, diarrhoea, flatulence, nausea and heart palpitations5</li><li>Vitamin C: doses greater than the tolerable upper intake level (UL) of 2000 mg per day can increase the risk of significant adverse effects such as osmotic diarrhea and GI upset15</li><li>Zinc: Mild gastrointestinal distress may occur with doses of zinc 50-150 mg/d16</li></ul> Key interactions Vitamin E <ul><li>Cisplatin: vitamin E may decrease the incidence and severity of neurotoxicity caused by cisplatin. Interaction is likely. Use with caution under supervision of a HCP and monitor</li><li>Nitroglycerine: vitamin E may prevent nitrate tolerance when given concurrently with transdermal nitroglycerin. Interaction is possible. Use with caution under supervision of a HCP and monitor</li><li>Orlistat: vitamin E absorption may be decreased. Interaction likely. Assess nutrient status and supplement if indicated. Interaction may be minimised by separating dose of medication and vitamin E by at least 2 hours</li><li>Anticoagulants and antiplatelet agents: vitamin E may increase risk of bleeding. However, conflicting data clinical studies have found no interaction with warfarin or aspirin, or inhibition of platelet aggregation. Case reports of interaction with warfarin and reduced clotting exist. Interaction is unlikely. Use with caution under supervision of a HCP and monitor</li><li>Vitamin C </li><li>Aluminium-containing antacids: increases drug side effects. Vitamin C chelates aluminium and increases aluminium absorption. To avoid interaction separate dose of medication by at least 2 hours17</li><li>Antihypertensive drugs: may have an opposing effect to drug. A clinical trial 6 week in duration with a treatment of both vitamin C 500mg and grape seed extract 1000mg increased blood pressure in hypertensive patients. Interaction is possible. Avoid combination of vitamin C and grape seed extract with hypertensive patients17</li><li>Desferrioxamine: opposing drug effect. Vitamin C may cause transient deterioration of cardiac function with desferrioxamine, avoid concomitant use17</li><li>Estrogen: may increase blood levels of drug. Possible interaction. Use with caution under supervision of HCP17</li><li>Paracetamol: high doses of vitamin C (&gt;3g) may decrease the elimination rate of paracetamol. Possible interaction. Use with caution under supervision of HCP17</li><li>Protease inhibitors: decrease drug effect. Use with caution under supervision of HCP17</li><li>Zinc </li><li>ACE inhibitors, angiotensin receptor blockers, and thiazide diuretics: urinary zinc excretion may be increased with long-term use of these drugs (decreasing zinc). Interaction is possible. Assess nutrient status and supplement if indicated17</li><li>Cefalexin: zinc may decrease the absorption of the drug by chelating with the drug. Interaction is possible. The interaction may be minimised by separating the dose of zinc at least 3 hours after taking cephalexin17</li><li>Hypoglycaemic drug: low zinc status is common in diabetic patients. Zinc supplementation and normalisation of zinc levels have been shown to improve glycaemic control. Assess nutrient status and supplement if indicated. Monitor blood glucose level and alter drug dose if required under the supervision of a HCP17</li><li>Integrase inhibitors: may decrease the blood level of the drug by chelating with the drug. Interaction is likely. Avoid concomitant use17</li><li>Penicillamine: zinc may decrease the activity of penicillamine. Interaction is possible. The interaction may be minimised by separating the dose of medication and zinc by at least 2 hours17</li><li>Tetracycline &amp; quinolone antibiotics: zinc may decrease the absorption and blood levels of these drugs. Interaction is possible. The interaction may be minimised by taking tetracycline at least 2 hours before, or 4-6 hours after zinc supplement17</li></ul> </li></ul><h2>LUTEIN AND ZEAXANTHIN (LZ)</h2>Mechanism of action<ul><li>LZ are related carotenoids found in the eye. The eye contains a higher concentration of LZ than any other tissue14,15</li><li>They are deposited in the macula where they form the macular pigment which may help protect the eye from light-induced damage16</li><li>They also act as antioxidants14</li></ul>ResearchThe Age-Related Eye Disease Study 2 (AREDS2) is one of the only studies for which there is good, long-term evidence for the benefits of high dose nutrients for people diagnosed with AMD.1 AREDS2 investigated LZ and/or omega-3 fatty acids EPA and DHA added to the original AREDS formula on progression to advanced AMD. Additionally, it assessed different forms of the original supplement with reduced zinc or no betacarotene.13Subgroup analysis found participants with the lowest levels of LZ in their diet, had a decreased risk of progression to advanced AMD with LZ supplementation.Dosage<ul><li>Lutein 10 mg/day18</li><li>Zeaxanthin 2 mg/day18</li></ul>Adverse effects<ul><li>Unlikely to cause adverse effects at recommended doses16</li></ul>Interactions<ul><li>No clinically significant interactions noted in the literature</li></ul>

Primary

<h2>Secondary recommendations</h2><h2>Omega-3 fatty acids</h2>Whilst AREDS2 did not find benefit for omega-3 supplementation, observational studies have suggested that higher dietary intakes of EPA/DHA may help to reduce the risk of AMD.19,20 They may also benefit dry eye.21

Secondary

<h2>Diet and lifestyle</h2><ul><li> Decrease foods that may increase risk: red meat2, trans fat3,4, vegetable oils (not olive)5, processed baked goods4, alcohol &gt; 3 drinks per day5 </li><li>Increase foods that may decrease risk: fish and omega-3 fatty acids3,6,7, olive oil3, nuts7, dietary carotenoids and antioxidants (found in brightly-coloured fruit and vegetables)5, low glycaemic index (GI)8</li><li>Increase foods rich in lutein and zeaxanthin: include green vegetables, egg yolk, kiwi fruit, grapes, zucchini, squash, pistachio nuts and corn22</li><li>Weight management: overall and abdominal obesity increases risk for progression to advanced AMD9,10</li><li>Physical activity decreases risk of AMD5,9</li><li>Quit smoking. Smokers are 3-4x more likely to develop MD, and may develop the disease 5-10 years earlier.1 There is good evidence that causally associates AMD and smoking.5</li></ul>

Diet & lifestyle

<h2>References</h2>1. Australian Heart Foundation. Guide to management of hypertension 2008. Updated 2010. 2. Sarris J, Wardle J. Clinical Naturopathy 2e. An evidence-based guide to practice. Chatswood: Elsevier, 2014 3. Huang N. Lifestyle management of hypertension. Australian Prescriber 2008;31(6):150-53. 4. US Department of Health &amp; Human Services. Dash eating plan. Accessed 02/02/2016 http://www.nhlbi.nih.gov/health/healthtopics/topics/dash/ 5. Australian Heart Foundation. Position Statement. Fish, fish oils, n-3 polyunsaturated fatty acids and cardiovascular health. 20086. Natural Medicines 2016. Fish oil professional monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=993 7. Braun L, Cohen M. Herbs and Natural Supplements. 4th edition. Chatswood: Elsevier, 2015. 8. Reid K, Frank OR, Stock NP, Fakler P, Sullivan T. Effect of garlic on blood pressure: a systematic review and meta-analysis. BMC Cardiovasc Disorder 2008;8:13 9. Reinhardt KM, Coleman CI, Teevan C, Vachhani P, White CM. Effects of garlic on blood pressure in patients with and without systolic hypertension: a meta-analysis. Ann Pharmacol 2008;42:1766-71 10. Miller PE, Van Elswyk M, Alexander DD. Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomised controlled trials. Am J Hypertens 2014;27(7):885-96. 11. Blackmores Institute 2015. Complementary Medicines Interactions Guide 7th ed. 12. Rosenfeldt F, Haas S, Krum H, Hadj A, Ng K, Leong J, Hohgson J, Watts G.Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Human Hypertens 2007;21:297-306 13. Ho MJ, Bellusci A, Wright JM. Blood pressure lowering effi cacy of coenzyme Q10 for primary hypertension. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD007435. DOI: 10.1002/14651858.CD007435.pub2. 14. Oregon State University, Linus Pauling Micronutrient Information Center 2016 Magnesium http://lpi.oregonstate.edu/mic/minerals/magnesium 15. Sontia BS, Touyz. Role of magnesium in hypertension. Arch Biochem Biophys 2007;458:33-3916. Braun L, Cohen M. Herbs and Natural Supplements 4th ed. Elsevier 201517. Blackmores Institute Complementary Medicine Interactions Guide 7th ed. 201518. Macular Disease Foundation 2014. Nutrition and Supplements for Macular Degeneration19. San Giovanni JP. Age-Related Eye Disease Study Research Group. The relationship of dietary lipid intake and age-related macular degeneration in a case-control study: AREDS Report No. 20. Arch Ophthalmol 2007;125(5):671-920. Johnson EJ. Potential role of dietary n-3 fatty acids in the prevention of dementia and macular degeneration. Am J Clin Nutr 2006;83(6 Suppl):1494S1498S. PMID: 1684185921. Kangari H. Short-term Consumption of Oral Omega-3 and Dry Eye Syndrome. Ophthalmol 2013;120:2191-219622. Natural Medicines Database. Lutein monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs supplements/professional.aspx?productid=754 Downloaded 26 February 2019

Age-related macular degeneration

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