Mini-Review - 'Long-chain Omega-3 Fatty Acids for Visual Acuity and the Prevention/Management of Ocular Disorders'

Very high levels of the long-chain omega-3 fatty acid, notably DHA (docosahexaenoic acid, 22:6 n-3), are found in the retina and macula of the eye wherein its presence supports optimal visual acuity by various mechanisms. In the photoreceptor cells, DHA is present in the membrane phospholipid component and provides ‘fluidity’ and other unique structure-function relationships along with mediating neuroprotective mechanisms. Research has indicated that a tissue insufficiency of DHA is associated with disturbances in retinal function. The metabolic conversion of the major dietary omega-3 fatty acid as the short-chain plant-derived LNA (alpha-linolenic acid, 18:3 n-3) to DHA is very limited in animals and humans. Thus, the direct intake of DHA itself via food sources (mainly fish/seafood or selected enriched foods) or via nutritional supplements is the most efficient way to provide optimal levels of tissue DHA. DHA intakes are very low in North America due to the minimal intakes of fish/seafood. DHA supplementation has been found to improve visual processing deficits in some studies.

A major Canadian population study (1) reported upon the long-term effect of omega-3 fatty acid intake during gestation and the subsequent visual development in Inuit children eleven years later. Interestingly, higher prenatal intakes of DHA from fish and marine mammals resulted in correspondingly higher levels of cord blood DHA and better visual system function in the school-age children. The randomised clinical trials reported to date which employed varying doses and durations of long-chain omega-3 fatty acid supplementation during pregnancy have not provided conclusive evidence for visual acuity benefit for the offspring. However, numerous studies have reported positive correlations between blood levels of DHA and improved visual function outcomes in breastfed and formula-fed infants. The latter studies have often employed DHA levels close to the average found in worldwide human milk (0.32 % of milk fat). DHA intakes via food and/or supplementation of at least 1400 mg/week (average of 200 mg daily) by the lactating mother would be expected to provide breast milk levels of DHA of at least 0.32 % of milk fat. A recent review (meta-analysis) evaluated the effect of long-chain omega-3 supplementation of infant formula (versus no such addition) on infant visual acuity (2). Based on 19 studies involving 1949 infants, a significant benefit of omega-3 supplementation in improving visual acuity was found at the age of 2, 4, and 12 months. Clinical evidence for a visual benefit of omega-3 supplementation in older subjects is mostly lacking although a small 90-day supplementation trial in subjects aged 45-77 years found a significantly better right eye visual acuity in participants with corrected vision receiving 312 mg supplemental DHA/EPA daily relative to controls.

Several population studies have studied the risk/incidence of various ocular disorders in relation to the long-term dietary intake of long-chain omega-3 fatty acids as DHA plus EPA (eicosapentaenoic acid, 20:5 n-3) from fish/seafood. Higher intakes of fish (as tuna) and omega-3 fatty acids amongst women aged 45-84 years was associated with a significantly lower risk for clinically-diagnosed dry eye syndrome (3). The prospective Nurses’ Health Study in the US (4) followed 71,083 women for up to 16 years and found that three or more servings of fish/week significantly reduced the risk for cataract extraction as did EPA/DHA intakes at 0.21 % of energy (versus only 0.05 of energy %). It is noted that an intake at 0.21 energy % is the equivalent of approximately 500 mg EPA plus DHA daily – which is much higher than the average daily intake of only 110 – 150 mg EPA/DHA. Other population studies on elderly subjects have found a protective effect of fish/shellfish intake against advanced AMD (age-related macular degeneration). Subjects consuming higher daily intakes of EPA plus DHA (approaching 500 mg daily) and those with higher circulating levels of EPA/DHA exhibited a significantly lower risk for late neovascular age-related maculopathy (5). These aforementioned population studies have supported the potential benefit of sustained long-term intakes of EPA/DHA in reducing the risk of developing certain ocular conditions. These have generated interest in testing the potential benefits of EPA/DHA supplementation in helping manage patients with specific ocular disorders.

AMD is a clinical condition that usually affects older adults with a loss of vision in the central portion of the visual field due to damage to the retina of the eye. The so-called ‘dry’ form of AMD involves the accumulation of debris (referred to as ‘drusen’) which can cause the retina to become attached. In view of the known anti-inflammatory potential of EPA/DHA and indications that local inflammatory processes play a role in AMD, it has been of interest to conduct controlled clinical trials to test the potential efficacy in helping to manage AMD. The AREDS2 Study (age-related eye disease Study 2) was a randomized clinical trial on 4203 subjects (aged 50-85 years) at high risk for progression to advanced AMD who were followed for at least 5 years while receiving daily supplementation with omega-3 (1000 mg EPA/DHA) and/or lutein-zeaxanthin or placebo (6). The results indicated a significant protective benefit against progression to advanced AMD with supplemental lutein-zeaxanthin in those subjects with the lowest background dietary intakes of these antioxidant carotenoids while EPA/DHA was without apparent benefit. It is of interest to note the publication of a recent supplementation trial (7) conducted in patients with dry AMD using much higher daily doses of EPA/DHA (5000 mg/day) over a 6 month period. This pilot study reported a significant improvement in vision acuity in all the patients with omega-3 supplementation within 4.5 months of supplementation based on the number of lines gained on reading charts. This recent study raises important questions and future research as to whether higher doses of supplemental EPA/DHA than often employed in past clinical trials may offer benefit (or enhanced benefit) in selected clinical conditions.

Dry eye disease (dry eye syndrome, DES) is a prevalent ocular condition globally and a frequent reason for seeking eye care. This inflammatory condition often leads to ocular discomfort as a most prominent patient complaint along with stinging, burning sensation, and visual disturbance with contributing factors including extensive computer viewing plus smoky and dusty environments. A number of controlled clinical trials have been reported recently on the improvements in DES symptoms in patients given EPA/DHA supplementation. As one example, DES patients receiving 1785 mg EPA/DHA daily (1245 mg EPA plus 540 mg DHA) for a 12-week period experienced a significant improvement in the visual analog scale score of eye pain (relative to the control group) along with significant improvements in other parameters (8). Very recently, a series of three published trials have appeared from the same research group showing considerable benefit in the alleviation of DES symptoms in patients with computer vision syndrome (9), in contact lens wearers (10), and in young and middle-aged visual display terminal users (11). The daily doses of EPA/DHA in this series of trials have ranged from 600-2400 mg daily with durations from 45 days to 6 months. Studies in animal models with DES have indicated that the decrease in inflammation with supplemental EPA/DHA is due partly to the production of novel lipid mediators known as ‘resolvins’ and ‘protectins’ formed from these long-chain omega-3 fatty acids and their ability to resolve inflammation.

Further information from evidence-based studies on the potential benefits of EPA/DHA in these and other conditions can be found at www.dhaomega3.org .

References

• Jacques, C. et al., J. Pediatr. 2011: 158 (1): 73-80.
• Qawasmi, A., A. Landeros-Weisenberger, and M. H. Bloch., Pediatr. 2013: 131(1): e262-e272.
• Miljanovic, B. et al., Am. J. Clin. Nutr. 2005: 82(4):887-894.
• Lu, M. et al., Am. J. Epidemiol. 2005: 161 (10): 948-959.
• Merle, B. M. J. et al., Invest. Ophthalmol. Vis. Sci. 2014: 55: 2010-2019.
• Age-related Eye Disease Study 2 Research Group., J. Am. Medical Assoc. 2013 : 309 (10): 2005-2015.
• Georgiou,T. et al., PharmaNutrition . 2014: 2(1): 8-11.
• Kawakita, T. et al., Biomed. Res. 2013: 34(5): 215 - 220.
• Bhargava, R. et al., Contact Lens and Anterior Eye. 2015: 38(6): 206-210.
• Bhargava, R. and P. Kumar., Cornea. 2015: 34(4): 413-420.
• Bhargava, R., P. Kumar, and Y. Arora., Eye Contact Lens. 2016: 42: 231-236.