Lưu ý. Không có những nghiên cứu này bao gồm adjunctive chất chống oxy hóa để ngăn chặn sự gia tăng căng thẳng oxy hóa. aThe kết quả đo chính là tiêu cực. Tuy nhiên, những người tham gia vào ALA vẫn còn trong nghiên cứu lâu hơn và có sự chậm trễ các tác dụng phụ so với dầu ô liu. | Nonpharmacological Biological Treatment 159 TABLE . A Summary of Controlled Omega-3 Fatty-Acid Clinical Trials in Participants with Bipolar Disorder Author year Stoll et al. 1999 Keck et al. 2006 Frangou et al. 2006 Gracious et al. 2006 Agent Fish oil EPA and DHA Ethyl-EPA Ethyl-EPA Flax oil alphalinoleic acid Dose grams 6 grams 1 or 2 grams 6-12 grams Comparator Olive oil Liquid paraffin Liquid paraffin Olive oil Number ages 30 18-65 120 18-70 75 18-70 40 6-18 Duration of trial 4 months 4 months 12 weeks 16 weeks Result Positive Negative Positive bipolar depression Negative Note. None of these studies included adjunctive antioxidants to prevent increases in oxidative stress. The primary outcome measure was negative. However participants on ALA remained in the study longer and had delays to adverse events compared with those on olive oil. One potential issue with this study is that some patients may not be able to transform ALA to eicosapentaenoic acid EPA and DHA the more biologically active omega-3s see Figure . The elongase and desaturase enzymes needed to accomplish this transformation have been considered potential genetic abnormalities in patients with serious mental illnesses. A second concern with this study is that the use of olive oil as a placebo may also confound results. Olive oil is a monounsaturated fat and likely has positive effects on cell membrane dynamics and possibly in turn brain function. Third there is some evidence that there is a therapeutic window for omega-3 fatty acids of between 1 and 2 grams per day. Higher doses without the benefit of antioxidants have been shown to be pro-oxidant Song Miyazawa 2001 Vericel et al. 2003 . This means that high doses may actually worsen the fatty-acid metabolism status of a patient. Previous studies had found 2 g day of ethyl-EPA to be the optimal dose for schizophrenia Peet Horrobin 2002 and 1 g day for unipolar depression Peet Horrobin Ethyl-Eicosapentaenoate Multicentre Study Group 2002 .
