Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in North America, Europe, and developed countries worldwide.
Nutrition may play an important role in the development and progression of AMD. There have been several epidemiological studies suggesting that omega-3 fatty acids could have a protective role in AMD, but a beneficial effect remains to be demonstrated in randomized controlled trials. There also exists a substantial body of evidence suggesting that protection against AMD may be provided by specific micronutrients (vitamins and minerals and antioxidants). The identification of risk factors for the development and progression of AMD is of particular importance for understanding the origins of the disorder and for establishing strategies for its prevention. We have examined the relationship between
dietary omega-3 intake and the incidence and progression of AMD, as well as the role of omega-3 supplementation in the prevention of the disorder, and also explored the role of other micronutrients in AMD.
AMD causes the macula, the small central area of the retina that controls visual acuity, to deteriorate.
While only a small part, the macula is more sensitive to detail than the rest of the retina—it is what helps you focus on small details such as threading a needle. Symptoms include blurriness, dark areas or distortion, and even permanent loss of the peripheral vision. Although the pathogenesis of AMD
remains unclear, current evidence suggests a multifactorial aetiology.
THE POTENTIAL ROLE OF OMEGA-3 FATTY ACIDS
Omega-3 and omega-6 fatty acids are important components of tissue lipids, particularly cell membrane phospholipids. The major dietary omega-3 polyunsaturated fatty acid is docosahexaenoic acid (DHA). This makes up only a small fraction of the fatty acids in most tissues, but is present at high levels in the retina, where it is a major structural lipid. As a result of its biophysical and biochemical properties, DHA may affect the permeability, fluidity, thickness, and lipid phase properties of the photoreceptor membrane, and may also be involved in signaling cascades, acting to enhance activation of membrane-bound retinal proteins and may be involved in rhodopsin regeneration. There is evidence that tissue DHA insufficiency is associated with changes in retinal function.
Eicosapentaenoic acid (EPA), the precursor to DHA as well as other major dietary omega-3 fatty acids, can exert similar actions to DHA. Dietary omega-3 fatty acids have also been shown to be beneficial in inflammatory diseases and where those taking omega-3 report less joint stiffness, swelling, tenderness, and fatigue.
Dietary omega-3 fatty acids have been shown to reduce the inflammatory response by competing with arachidonic acid metabolism and altering the eicosanoid profile. EPA and DHA have been shown to decrease CD4+ T-cell activation and cause the inflammatory environment to switch from a pro-inflammatory to an anti-inflammatory one. These anti-inflammatory actions may be beneficial in the retina as inflammation may play a role in the development of new choroidal vessels in exudative AMD. Early studies investigating a potential relationship between dietary fat intake and AMD revealed that this might not be straightforward.
Results of initial studies suggested that higher intake of some fatty acids, and possibly elevated blood cholesterol levels, may be related to an increased risk of AMD. More specifically, results suggested that higher intake of specific subtypes of lipids (cholesterol, monounsaturated, polyunsaturated fats, omega-6 fatty acid, linoleic acid) rather than total fat intake may be associated with a greater risk for progression of AMD. In contrast, diets high in omega-3 fatty acids and fish were found to be inversely associated with risk for AMD when intake of linoleic acid was low.
Since this time, there have been several epidemiological studies suggesting that omega-3 or polyunsaturated fatty acids DHA and EPA could have a protective role in AMD, particularly exudative AMD. Furthermore, there is evidence to suggest that omega-3 fatty acids have cytoprotective and cytotherapeutic actions, giving rise to anti-angiogenic and neuroprotective mechanisms within the retina. (An angiogenesis mechanism inhibits the growth of new blood vessels.)
With a number of studies suggesting that the type of fat intake may influence risk for advanced AMD, as well as reported evidence of a relationship between fat intake and earlier stages of maculopathy, researchers further explored the potential association between specific types of dietary fat and risk for advanced AMD.
In a multicenter eye disease case-control study, 349 individuals with advanced, neo- vascular AMD and 504 controls without AMD, but with other ocular diseases, were included. Similar to findings from the Nurses’ Health Study and the Health Professionals Follow-up Study, this case-control study found that higher intake of omega-3 fatty acids was associated with a lower risk for AMD among individuals consuming diets low in linoleic acid.
The findings from this study are not conclusive as data are subject to reporting and other biases and were not adjusted for all potential confounding factors such as family history of AMD. Subsequently, researchers conducted a prospective cohort study in 261 participants with some sign of nonexudative AMD and found that, in these high-risk subjects, higher fish intake was associated with a lower risk of AMD progression among subjects with lower linoleic acid intake.
OMEGA-3 SUPPLEMENTATION FOR AMD
There have only been a few clinical trials conducted to investigate the role of omega-3 fatty acid supplementation in the prevention of AMD. The French Nutritional AMD Treatment phase 1 (NAT-1) study evaluated the feasibility of a prospective study of oral DHA and EPA supplementation in AMD.
In this study, a group of 38 patients with drusenoid pigment epithelial detachment (DPED) in one eye without choroidal neovascularization (CNV) received DHA and EPA (EPA: 720 mg/day and DHA: 480 mg/day) or placebo for six months. There were significant increases in serum and RBCM EPA and DHA levels at the six-month visit in the group receiving the oral supplement, with no changes in the control group, despite dietary recommendations. Although there were no benefits in terms of AMD progression in this study, the supplement was well-tolerated. The vast majority of evidence suggesting a positive effect of dietary omega-3 intake on the development and progression of AMD comes from observational studies.
Although this body of evidence is promising, a beneficial effect of omega-3 fatty acids in AMD remains to be demonstrated in randomized controlled trials. Given that the risk of taking omega-3 fatty acids from dietary fish or fish oil supplements is low, however, the potential benefits can be considered to outweigh the risks, and consumption of fish or fish oil supplements can therefore be recommended.
COMMENTARY BY DR. SELENE WILKINSON, ND. AND DR. JASON BOXTART, ND.
In Canada, one million people have reported to have some form of AMD. While it usually affects people over 50, it can affect someone younger. The primary risk factors for AMD include increasing
age, ethnicity, and genetics. Smoking has also been linked as a modifiable risk factor in numerous studies.
While there is no cure, medications such as bevacizumad, ranibizumab, and aflibercept can block the growth of abnormal blood vessels. This may help partially recover vision. Photodynamic therapy is another way that can improve vision and reduce the rate of degeneration by activating a drug called verteporfin, which is injected into the arm, by shining a special light in the eye. There is also laser therapy and low vision rehabilitation. These, however, are all treatments used after developing AMD. The only proven supplement to aid in the prevention is omega-3.
There are many studies that document all of the benefits, including for eye heath, of omega-3s. Many have been conducted with daily supplemental dosages between 2 and 5 grams of EPA and DHA. In my own practice, I recommend supplementation of omega-3s to many patients for various conditions, as this would be more than you could get in the recommended two servings of fish per week. However, eating fish can still be beneficial as studies have documented that 60- to 80-year-olds eating fish more than twice a week were half as likely to develop macular degeneration as those who ate no fish at all.
Therefore, there are notable and traceable benefits of omega-3s for eye health in both a dietary and supplemental manner. “When looking for food sources that are rich in Omega-3s, salmon, herring, mackerel, rainbow trout, sardines, flaxseeds and walnuts could be good choices,” says Dr. Selene Wilkinson, ND, cofounder of Lemon Water Wellness.
While supplementing omega-3 is beneficial, there are several drug interactions to be aware of. These include aspirin, CoQ10, folic acid, vitamin B12, vitamin C, vitamin E, and some multivitamins. However, “the original AREDS study showed patients who were at moderate risk for progression with the highest omega-3 intake found a 30 per cent reduced risk of progression after 12 years,” states Dr. Jason Boxtart, ND. With the lack of pharmaceutical interventions for the treatment of AMD, omega-3 continues to be the leading preventative measure.
