Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the Nutritional AMD Treatment 2 study

Ophthalmology. 2013 Aug;120(8):1619-31. doi: 10.1016/j.ophtha.2013.01.005. Epub 2013 Feb 8.


Objective: To evaluate the efficacy of docosahexaenoic acid (DHA)-enriched oral supplementation in preventing exudative age-related macular degeneration (AMD).

Design: The Nutritional AMD Treatment 2 study was a randomized, placebo-controlled, double-blind, parallel, comparative study.

Participants: Two hundred sixty-three patients 55 years of age or older and younger than 85 years with early lesions of age-related maculopathy and visual acuity better than 0.4 logarithm of minimum angle of resolution units in the study eye and neovascular AMD in the fellow eye.

Methods: Patients were assigned randomly to receive either 840 mg/day DHA and 270 mg/day eicosapentaenoic acid (EPA) from fish oil capsules or the placebo (olive oil capsules) for 3 years.

Main outcome measures: The primary outcome measure was time to occurrence of choroidal neovascularization (CNV) in the study eye. Secondary outcome measures in the study eye were: incidence of CNV developing in patients, changes in visual acuity, occurrence and progression of drusen, and changes in EPA plus DHA level in red blood cell membrane (RBCM).

Results: Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA group (19.5±10.9 months and 28.4%, respectively) and the placebo group (18.7±10.6 months and 25.6%, respectively). In the DHA group, EPA plus DHA levels increased significantly in RBCM (+70%; P<0.001), suggesting that DHA easily penetrated cells, but this occurred unexpectedly also in the placebo group (+9%; P = 0.007). In the DHA-allocated group, patients steadily achieving the highest tertile of EPA plus DHA levels in RBCM had significantly lower risk (-68%; P = 0.047; hazard ratio, 0.32; 95% confidence interval, 0.10-0.99) of CNV developing over 3 years. No marked changes from baseline in best-corrected visual acuity, drusen progression, or geographic atrophy in the study eye were observed throughout the study in either group.

Conclusions: In patients with unilateral exudative AMD, 3 years of oral DHA-enriched supplementation had the same effect on CNV incidence in the second eye as did the placebo. However, RBCM fatty acid measurements revealed that CNV incidence was significantly reduced in DHA-supplemented patients showing a steadily high EPA plus DHA index over 3 years.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Capsules
  • Dietary Supplements
  • Docosahexaenoic Acids / administration & dosage*
  • Double-Blind Method
  • Drug Combinations
  • Eicosapentaenoic Acid / administration & dosage*
  • Female
  • Fluorescein Angiography
  • Humans
  • Lipids / blood
  • Male
  • Middle Aged
  • Prospective Studies
  • Retinal Drusen / diagnosis
  • Retinal Drusen / prevention & control*
  • Retinal Drusen / therapy
  • Visual Acuity / physiology
  • Vitamin E / administration & dosage*
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / prevention & control*
  • Wet Macular Degeneration / therapy


  • Capsules
  • Drug Combinations
  • Lipids
  • Vitamin E
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid