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Nutrition and AMD

Kreissig Lecturer reviews evidence for supplements and healthy diet

Howard Larkin

Posted: Saturday, October 1, 2016

kreissiglecture_chew_kreissig_2093

Dr Emily Y Chew, who delivered the prestigious Kreissig Lecture at the 16th EURETINA Congress in Copenhagen, with Prof Ingrid Kreissig

Strong evidence suggests that targeted nutritional supplements can slow progression of age-related macular degeneration (AMD) in patients with bilateral intermediate disease and unilateral late disease, but have no effect for patients with earlier-stage AMD or a family history of the disease, according to a leading researcher for the American National Eye Institute (NEI).
Observational studies also suggest a diet rich in fish and leafy green vegetables may reduce the incidence of AMD and slow its progression. “I want to say – and this is very true – we are what we eat,” said Emily Y Chew MD in her recent Kreissig Lecture at the 16th EURETINA Congress in Copenhagen, Denmark.
And while research through the international AMD Gene Consortium has made great progress in identifying AMD genotypes, so far no actionable differences in response to existing supplements have been identified, Dr Chew said. This makes the cost and risk of routine genetic testing hard to justify, she added. “We are not ready to change the recommendation from the American Academy of Ophthalmology task force that suggests avoiding genetic testing of AMD patients, at least for now. We need further studies on this.”

SAFER SUPPLEMENT
The initial supplement formula validated by the Age-Related Eye Disease Study (AREDS) contains vitamin C (500mg), vitamin E (400IU), beta-carotene (15mg), zinc oxide (80mg) and cupric oxide (2mg), and resulted in a 25 per cent reduction in risk of progression to late AMD in five years (Arch Ophthalmol. 2001;119(10):1417-36).
Notably, the full combination had beneficial effects that individual components did not. However, it was not recommended for smokers since beta-carotene increases the risk of lung cancer.
Evidence for the more effective revised supplement combination comes from the massive Age-Related Eye Disease Study 2 (AREDS2), Dr Chew said. AREDS2 found that replacing beta-carotene with lutein/zeaxanthin (L/Z) (10mg/2mg) incrementally reduced the chances of AMD progression compared with the original AREDS formula, while eliminating the carcinogenic risk of beta-carotene – which the study 
also found doubled the lung cancer incidence overall, with former smokers particularly susceptible.
AREDS2 also tested the effects of adding omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), but found no effect on AMD progression. A lower zinc oxide dose, 25mg, was also tested and no difference was found from the original 80mg. The resulting formula recommended based on AREDS2 is vitamin C (500mg), vitamin E (400IU), L/Z (10mg/2mg), zinc oxide (80mg) and cupric oxide (2mg). (JAMA. 2013;309(19):2005-15)
The AREDS2 supplement formula is both safer and more effective than the original for slowing AMD progression in patients with intermediate disease, defined as large drusen in both eyes, or late disease, but not for patients with early disease or no disease, Dr Chew noted. The public health benefits from both formulae continue to accrue, she added.

DIETARY EVIDENCE
Despite the negative results for omega-3 supplements, evidence suggests dietary intake of these nutrients is important, Dr Chew said. Observational studies strongly suggest that high dietary intake of total omega-3 long-chain polyunsaturated fatty acids found in fish such as salmon and trout, as well as high dietary intake of L/Z found in spinach, kale and collard greens, is associated with reduced incidence of AMD and reduced progression from bilateral drusen to central geographic atrophy (GA) over six years. (Arch Opththalmol 2007;125:671-67)
Higher total DHA and EPA also 
were associated with slower progression of bilateral drusen to central GA over 6.3 years. (Arch Ophthalmol 2008;126(9):1274-1279)
Ancillary studies found AREDS2 supplements also had no discernible effect on cardiovascular disease (JAMA Intern Med. 2014 May;174(5):763-71), yet observational studies suggest dietary sources may be important here as well, Dr Chew said. “Essentially most trials of omega-3 LCPUFAs have been negative. Patients are still encouraged to eat fish rather than take supplements for cardiovascular disease.”
Observational studies associate nutritional factors, especially fish consumption, with cognitive function, and cognitive function is associated with AMD, Dr Chew noted. These findings also emphasise the importance of a healthy diet in reducing AMD risk, she said.
Emily Y Chew: echew@nei.nih.gov