# The Protective Effect of Polyunsaturated Fatty Acids against Dry Eye Disease: A Literature Review
## 4 Current Perspectives
However, an adequate consumption of EPA + DHA is not easily achievable with dietary intake alone [29], because the processing and cooking of food results in a substantial loss and denaturation of the PUFAs [97]. In addition, only a small fraction of PUFAs can be converted to anti-inflammatory molecules during in vivo metabolism [29]. Hence, oral supplementation using an extract formula, such as compound capsules, may be more effective for achieving the therapeutic dose of \(\omega\)3 PUFAs [29,96]. The intake of fish oil capsules, the most common formula for \(\omega\)3 PUFA supplements, can sometimes cause adverse effects, including nausea, regurgitation, and fish-tasting aftertaste [93]. Fish allergy may be a contraindication for fish oil supplements [88,93]. Vegetable sources of PUFAs, including primrose or flaxseed oil, can be recommended for these patients [88,96]. Despite the potential health benefits, precautions are necessary because the administration of high-dose \(\omega\)3 PUFAs (over 2000 mg EPA + DHA per day) can be associated with several health risks [89]. The intake of an excessive amount of \(\omega\)3 PUFAs can be associated with an increased risk of hemorrhage due to its potential antithrombotic effect, and it may be contraindicated in patients with a bleeding tendency [31,89]. Therefore, medical advice is necessary for patients with hematologic disorders and liver and cardiovascular diseases before commencing \(\omega\)3 PUFAs supplementation [89]. High blood levels of long-chain \(\omega\)3 PUFAs, i.e., EPA and DHA, could be associated with a higher risk of prostate cancer [89,98]. As fish oils are also rich in fat-soluble vitamin A, long-term supplementation with an excessive dose of fish oil capsules can lead to hypervitaminosis A, which can cause hyper-calcemia and osteoporosis due to increased bone turnover [96]. Both the FDA in the USA and the National Health and Medical Research Council in Australia have recommended that the consumption of up to 3000 mg (3 g) of \(\omega\)3 PUFAs per day, derived both from dietary intake and supplements, may be safe [89,93]. It should also be noted that seafood can be affected by ocean pollution, and coldwater fish, the main source of \(\omega\)3 PUFAs, can accumulate toxins (e.g., mercury and dioxins) in their body as they are located at the upper levels of the food chain in the ocean [88]. Hence, FDA has recommended that the intake of a large amount of fish that may contain increased levels of toxins including mercury, e.g., swordfish, marlin, shark, king mackerel, and bigeye tuna, should be avoided [88]. Nonetheless, FDA recommends the consumption of \(\geq\)8 ounces (227 g) of seafood every week for American adults, and also advises that the consumption of seafood containing relatively low levels of mercury, e.g., salmon, sardine, herring, cod, haddock, anchovy, oyster, scallop, shrimp, and canned light tuna, up to 12 ounces (340 g) per week may be safe [88]. Although this literature review has a limitation that systematic analysis or meta-analysis of the results of the studies were not performed, we believe this review may provide readers with new information as the results of the studies recently reported was introduced [34,36,37,38,42,60,61,62,74,75,83,85], This review also included the results of experimental studies [47,48,49,50]. For the evaluation of the influence of PUFAs on DED, conventional objective tests, such as TBUT, Schirmer test, and corneal stain score and subjective tests, such as questionnaire for dry eye symptoms have been commonly used. However, these tests show limited reproducibility, which might influence the inconsistency of the outcomes among the studies with similar designs [99]. Discrepancy between sign and symptoms often observed in DED might also be associated with contradictory outcomes [99,100].