Abstract
Abstract: :
Purpose:Patients with XLRP were nutritionally supplemented with the omega-3 fatty acid, DHA, in a placebo-controlled, randomized clinical trial. As a part of this trial, we assessed the incorporation of DHA and its interaction with omega-6 fatty acids in blood lipids. Methods:Male patients diagnosed with XLRP (mean age=16 ± 9yr; range=4-38yr) were randomized to groups receiving capsules containing DHA-enriched oil (400 mg DHA/day; n=23) or a corn/soy oil placebo (n=21). Male volunteers (n=20; age 17 ± 7yr) with normal vision provided normative fatty acid data. Blood samples were collected at enrollment and throughout the 4-yr trial at 6-month intervals. Fatty acids from total plasma lipids, total red blood cell (RBC) lipids, RBC-phosphatidylcholine (RBC-PC), and RBC-phosphatidylethanolamine (RBC-PE) were determined by capillary column gas chromatography. Results:At enrollment, the mean level of RBC-DHA in all patients was reduced by 35% compared to age- and sex-matched controls (27 vs 41 mg DHA/ml packed RBCs; p<0.0005). By 6 months, RBC-DHA levels were elevated 2.5-fold (68 mg/ml; p<0.0005) and remained at this level thereafter. DHA levels in plasma, RBC-PC, and RBC-PE were similarly elevated. By year 4, the levels of the omega-6 fatty acid, arachidonic acid, were significantly decreased by 10%, 16%, and 22% in total plasma, total RBCs, and RBC-PC but reduced by only 3% in RBC-PE. Conclusion:The differential distribution of arachidonic acid in RBC membrane phospholipids is consistent with selective acyl displacement due to omega-3/omega-6 fatty acid competition. The elevation of DHA levels in the circulation indicates that uptake and transport mechanisms for DHA are intact in patients with XLRP. However, since measures of DHA levels in viable human retina are unobtainable, indirect assessment of the role of DHA in this tissue will depend on its impact on retinal function following DHA nutritional supplementation.
Keywords: 562 retinal degenerations: hereditary • 492 nutritional factors • 357 clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials