The latest review of the science linking omega-3 intake to lower incidence of age-related macular degeneration (AMD) has concluded that the potential therapeutic benefit of omega-3 fatty acid supplementation is supported by the role of these fatty acids in normal retinal physiology, their anti-inflammatory properties, and the putative role of inflammation in AMD1. However, since oxidative stress has a recognised role in the development of AMD, and omega-3 fatty acids are susceptible to oxidation, this may partially masked their benefit. Therefore, co-supplementation with anti-oxidants will likely be necessary to reap the full benefits of omega-3 fatty acid supplementation. Currently a five year randomized, double-blind, placebo controlled clinical study including over 4000 people is underway to provide proof of that benefit (www.areds2.org).
AMD is a leading cause of vision loss affecting about 1.7 million people with an additional 7.3 million having early signs of the disease2. People in middle-age have about a 2 percent risk of getting AMD, but this risk increases to nearly 30 percent in those over age 752. In the United States, cases of AMD are expected to rise by about 50% over the next decade to reach 30 million by 20201. AMD gradually destroys sharp, central vision that is needed for seeing objects clearly and for common daily tasks such as reading and driving. It affects the macula, the part of the eye that allows you to see fine detail. It is located in the centre of theretina, the light-sensitive tissue at the back of the eye. The retina is comprised largely of DHA, a dietary omega-3 LC-PUFA that we consume primarily from fish. While the pathogenesis of AMD remains elusive, several risk factors have been established including age, smoking and certain genetic factors. In addition, atherosclerosis-like plaques associated with cardiovascular disease may also lead to AMD. Numerous population studies have shown that higher intake of fish and omega-3 LC-PUFAs, in particular docosahexaenoic acid (DHA) may be associated with reduced incidence of AMD. Given the public health importance of AMD, the results of this latest review article from Harvard Medical School, Boston, MA, the University of California Davis Eye Centre, Sacramento, CA and the Federal University of Sào Paulo, Brazil, are encouraging.
Not included in the review, was the strongest observational evidence to date that was published two months previous showing that increased intake of fish and fish derived omega-3 long chain polyunsaturated fatty acids (LC-PUFAs), significantly decreases the risk of developing AMD by up to 42 percent, 2. The study supported by a research grant from the National Institutes of Health and completed at Harvard Medical School, Boston, USA, included 38,022 women aged 45 years or older and initially free of AMD who were followed for over ten years. Eating habits were assessed at the start of the study to measure the quantity of fish and omega-3 LC-PUFAs including DHA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA), and yearly questionnaires and follow up medical examinations tracked the development of AMD. Following analysis of the data, participants were ranked into 3 groups depending on their intake of LC-PUFAs. Women who consumed the most DHA compared to women who consumed the lowest amount had a 38% lower risk of developing AMD. Higher EPA intake was associated with a 35% lower risk, DPA with a 25% lower risk and eating one or more servings of fish per week compared to less than one serving per month was associated with a 42% reduction.
Although results of randomised, controlled trials are still not available, these reports strongly indicate that DHA supplementation may prevent the onset and/or slow the progression of AMD and that combined with anti-oxidants may provide greater benefit.
- Kishan AU, Modjtahedi BS, Martins EN, Modjtahedi SP, Morse LS. Lipids and Age-related Macular Degeneration. Survey of Ophthalmology 2011;56(3):195-213.
- Christen WG, Schaumberg DA, Glynn RJ, Buring JE. Dietary ω- 3 fatty acid and fish intake and iincident age-related macular degeneration in women. Am J Clin Nutr Published ahead of print March 14, 2011, doi:10.1001/archophthalmol.2011.34.
Topics: Omega-3 fatty acids, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), long chain polyunsaturated fatty acids (LC-PUFAs), age-related macular degeneration (AMD), central geographic atrophy (CGA).
Objective: To examine the evidence for a role of omega-3 LC-PUFAs (EPA and DHA) singly and possibly combined with antioxidants to prevent AMD.
Background: AMD is the leading cause of severe visual impairment among individuals over 65 years old in the developed world. In the United States, cases of AMD are expected to rise by about 50% over the next decade to reach 30 million by 2020. While the pathogenesis of AMD remains elusive, several risk factors have been established including age, smoking and certain genetic factors. In addition, atherosclerosis-like plaques associated with cardiovascular disease may also lead to AMD. Previous population studies have shown that higher intake of fish and omega-3 LC-PUFAs may be associated with reduced incidence of advanced AMD, and a few studies have reported similar impact on early AMD. Given the public health importance of AMD, it is important to investigate the use of omega-3 LC-PUFAs for preventive measures.
Method: This review article highlighted the importance of DHA in retinal function, presented mechanisms whereby DHA supplementation may prevent AMD and summarized the clinical studies to date that demonstrating the role of DHA in AMD prevention.
A) DHA is more concentrated in retinal tissue than in any other mammalian cell membrane. The high susceptibility of DHA to oxidation due to its desaturation, its prolonged exposure to radiant energy within the eye, and the high oxygen consumption in the retina, suggest a possible role for oxidative stress in AMD pathogenesis and consequently antioxidant use as a preventative for the condition.
B) Accumulation of lipoproteins on the retinal pigment epithelium progresses with age and may be impacted by the predominate type of dietary fatty acids consumed
C) DHA & EPA produce anti-inflammatory, anti-oxidative, neuro-protective and survival factors for photoreceptor cells. Dietary supplementation with DHA singly or combined with anti-oxidants such as those included in the Age-Related Eye Disease Study (AREDS) (i.e. Vitamin C, E, beta-carotene and zinc) may slow progression of moderately severe early AMD or advanced AMD.
D) Dietary omega -3 fatty acid intake, fish consumption and nut consumption are protective towards AMD whereas high total fat and trans fat intake may increase risk.
The following summarizes results of population studies published to date.
- The Blue Mountain Eye Study found that higher fish consumption was associated with decreased odds of late AMD. There appeared to be a lower threshold for protection where higher levels of fish consumption did not confer greater benefit.
- The Nurses’ Health Study and the Health Professionals Follow Up Study found an inverse relationship between AMD risk and high intake of DHA and fish.
- A multi-centered case-control study reported that higher omega-3 fatty acid intake conferred a lower risk of neovascular AMD among those with a low linoleic acid (LA) intake.
- A cohort study found that fish intake was protective against AMD progression ONLY among those with low LA intake while higher total fat and vegetable fat – but not animal fat- intake increased the risk of AMD. The authors also concluded that consuming baked goods increased AMD risk two-fold while nuts were protective. Again, the fish had a threshold protective effect at about 2 servings of fish per week.
- The US Twin Study of an AMD population concluded that high omega- 3 intake conferred a preventive fraction of 22%.
- A prospective cohort study of the Icelandic population found that low herring intake protected against drusen development.
- Reanalysis of the Blue Mountain Study data showed that higher intake of total omega-3 fatty acids and Alpha-linolenic acid (ALA) were associated with decreased risk of AMD. Fish more than once per week protected against early AMD and intakes greater than 3 times weekly protected against late AMD.
- The POLANUT study showed that fatty fish intake more than once per month was protective when compared to fatty fish intake less than once per month.
- The EUREYE study showed that eating oily fish at least once per week and DHA & EPA intake protected against neovascular AMD.
- Data derived from the AREDS study showed that a higher intake of total omega-3 fatty acids, DHA, total fish and broiled /baked fish were protective towards neovascular AMD.
- A prospective cohort analysis of neovascular AMD and CGA development in patients with bilateral drusen indicated a reduced likelihood of progression to CGA, but not neovascular AMD among study participants with the highest EPA and DHA consumption.
- SanGiovannii et al. reported that higher intake of EPA, DHA and EPA+DHA protected against progression to either CGA or neovascular AMD.
- Chiu et al. reported that individuals with the highest intake of DHA and EPA had the lowest risk of progression to advanced AMD amongst a subgroup of AREDS participants. The authors suggested that DHA supplementation alone could be protective towards the development of early AMD, while co-supplementation with AREDS supplements may be beneficial in preventing progression to advanced AMD.
- A large prospective cohort from the Melbourne Collaboration Cohort Study showed that higher omega-3 fatty acid intake was inversely associated with early AMD.
- Tan et al. re-examined the Blue Mountain Eye Study population and found that one serving of fish per week was associated with reduced risk of early AMD and that protective effect was enhanced in patients with low LA consumption.
- Chong et al. pooled the data from 9 of the aforementioned studies, obtaining a total of 88,974 individuals, with 3202 cases of AMD. Altogether, the dietary intake of omega-3 fatty acids was associated with a reduced risk of both early and late AMD
Conclusion: Taken together, considerable empirical evidence supports a relationship between
dietary fat intake and AMD risk. However, in the absence of a randomised, controlled trial, definitive conclusions cannot be drawn. The potential therapeutic benefit of omega-3 fatty acid supplementation is supported by the role of these fatty acids in normal retinal physiology, their anti-inflammatory properties, and the putative role of inflammation in AMD. Oxidative stress has a recognised role in AMD, and the susceptibility of omega-3 fatty acids to oxidation may counteract their benefit. Therefore, co-supplementation with anti-oxidants will likely be necessary to reap the full benefits of omega-3 fatty acid supplementation. The pending results of the AREDS2 trial will hopefully provide more concrete answers regarding omega-3 supplementation efficacy.
Relevance to: Efalex Vision, Efalex Active 50+
Reference: Kishan AU, Modjtahedi BS, Martins EN, Modjtahedi SP, Morse LS. Lipids and Age-related Macular Degeneration. Survey of Ophthalmology 2011;56(3):195-213.